Study No.  5221.06
    TOXICTIY OF
IN

    Performed  for:

      Triaajle institute
    P.O. Box 12194
         Triangle Park
North Carolina   27709
 Revised Final Report

    Hareh 21,

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 50272-101
  REPORT DOCUMENTATION
         PAGE
1. REPORT NO.
  EPA/530-SW-88-027
3. Recipient's Accession No.
   PB88-197496/AS
 4, Title and Subtitle
            Subchronic Toxicity of  Ortho-Cresol in Sprague
            Dawley  Rats
                                                  5. Report Date
                                                    March  21, 1988
 7. Author(s)
            Dr. Dennis Dietz and Dr,  L. Thomas Mulligan
                                                                            8, Performing Organization Rep'- No.
 9, Performing Organization Name and Address
            Microbiological Associates,  Inc.
            5221  River  Road -  ™-   ~  "
            Bethesda, MD 20816
                                                  10. Project/Task/Work Unit No.
                                                  11. Contraet(C) or Grant(G) No.

                                                  
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                                                Study No. 5221.06
            SUBCHRQNIC TOXZCEEY OF OHIKXEESOL
                   IN SFKAGUE DAWIEY RATS
                   MAI Chemical No.: 23
    Sponsor:
      Sponsor
  Representative:
Research Triangle Institute
P.O. BOX 12194
Research triangle Park
North Carolina   27709
Dr. Dennis D. Dietz
Testing Facility?   Microbiological Associates Inc. (MBA)
                    5221 River Road
                    Bethesda, Mayland  20816
 Initiation Date:   September 16, 1985

 Completion Date:   December 18, 1985
                    L. Thomas wlligan, Tff.D.
                    study Director       '

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                                ACKNOWLEDGEMENT

     This report 1s submitted in partial fulfillment of the requirements of Work
Assignment No. 35, EPA Contract No, 68-01-7075.  This study was conducted by
Microbiological Associates, Incorporated as a subcontractor to Research Triangle
Institute (RTI).
     Dr. Dennis Dietz, formerly of RTI, was the work assignment leader.  Dr.
Reva Rubenstein of EPA was the work assignment manager and provided technical
direction and comment.  Dr, Ambika Bathija, also of EPA, provided review
comments and direction on the finalization of the report.

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                                                      Study No. 5221.06

                             TABLE "OF CONTENTS


                                                                     Page

  I.  SUMMARY			     1

 II.  INTRODUCTION.........				     1

III.  MATERIALS MD METHODS			     1

      A.  Test Article.	".......,	     1
      B.  Animals..	     1
      C.  Experimental Design		     2
      D.  Statistical Analyses.	..................	     6

 TV.  RESULTS.....					     6

      A.  Analyses and Stability of Dosage Form Preparations......     6
      B.  Mortality/Clinical Observations,	     6
      C.  Body Weight.	     7
      D.  Food Consumption.	     8
      E.  Clinical Pathology.	     8
      F.  Ophthalmology......	     8
      G.  Organ Weights	     9
      H.  Pathology	.'		........     9

  V.  DISCUSSION.	     9

 VI.  PERSONNEL	    10

VII.  ARCHIVES		...		    10


                                APPENDICES

      APPENDIX A - TWO-WEEK KANGE-FM^G/EXPDORATORY STUDY
                   OF OKIHO-CKESOL IN SPRAGUE DAWLEY RATS	.......   A-l

      APPENDIX B - ANALYTICAL CHEMISTRY METHODOLOGY.	   B-l

      APPENDIX C - CLINICAL PATHOLOGY METHODOLOGY		   C-l

      APPENDIX D - INDIVIDUAL ANIMAL DATA.		   D-l

      APPENDIX E - OPHTHALMOLOGY  REPORT.	   E-l

      APPENDIX F - PATHOLOGY REPORT	   F-l

      APPENDIX G - PROTOCOL,  AMENDMENTS,  AND  DEVIATIONS.	   G-l
               paginated per source
                                    \\f

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                                                          'Study No. 5221.06
   I.  SUMMERY:
       This  study examined the toxic effects of ortho-cresol in Sprague
Dawley rats  following 13 weeks of gavage administration.  Dose levels studied
were 0, 50,  175 and  600 mg/kg/day.   The biological effects of ortho-cresol
were generally restricted  to the  high dose level. ' Treatment-related central
nervous system depression  was apparent for these animals and probably
contributed  to their death.  On only one occasion and at no other tine,
reversible CNS depression  was also noted for two mid dose animals.  No other
toxic manifestations were  seen for ortho-cresol treated rats.  Thus,
175 rag/kg/day for ortho-cresol administered to male and female Sprague Dawley
rats for 13  weeks appears  to be the  dose at or below which no significant-
toxicological effects other than  transient weight and weight gain effects in
males and infrequent clinical signs  of tremors and cona were observed.


  II.  INTRODUCTION;

       This  study was conducted to assess the toxicity of ortho-cresol
(o-cresol)  in rats when administered for 13 weeks by gavage.  Ml methods and
procedures were conducted  in accordance with the appropriate Quality Assura-
nce Prograins (Microbiological Associates, Inc.; MBA or Pathology Associates,
Inc.? PAI)  designed  to conform with  FDA Good Laboratory Practice Regulations.


 III.  MATERIALS AND METHODS:

       A.   Test Article

           o-Cresol  (99.5%), 4 kg, was received on 07/29/85 and was assigned
           MBA chemical number 23.  The source was Eastman Kodak Company,
           Rochester, NY,  14650 (lot No. B12B).  The test article was stored
           in its original container at room temperature and ambient humi-
           dity.


       B.   Animals

           One-hundred and thirty Sprague Dawley rats of each sex were
           obtained  from Charles River Breeding laboratories, Inc., Lakeview
           (Newfeld), NJ on September 4, 1985.   The animals were approxi-
           mately five weeks old upon arrival at MBA's animal facility.  The
           animals were in quarantine/pretest for 12 days prior to initiation
           of treatment.   Housing was by groups during quarantine and
           individual during the treatment period.  The animals were housed
           on Beta-Chip hardwood bedding in polycarbonate cages which
           accommodated aniinals up to the upper weight range reccramended in
           the Guide_for the Care..and....Use of laboratory Animals,  EHEW, (NTH)
           No.  78.23.  All test animals received Purina Laboratory Chow No.

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                                                   Study No. 5221.06


     5001 in block form and water (Washington Suburban Sanitary
     Commission, Potomac  Plant) ad libitum.

     During the study period, animals were housed in a temperature-
     controlled room with a 12-hour light/dark illumination cycle.
     Animal room temperature and  humidity were recorded once daily and
     were noted to be outside of  the protocol-specified ranges on
     several occasions  during the study.  Monthly environmental data
     are  summarized below:
Month/Year
   9/85
  10/85
  11/85
  12/85
Number of
Readjms
   15
   31
   30
   17
Mean
± S.D.
TEMPERATURE
76.8 ± 2.6
78.7 ± 3.3
78.1 ± 2.8
73.8 ± 3.6
Rancre
(degrees F
74-82
70-85
72-82
67-79

a
')

Number (%) of Readings
 Within the Protocol-
	Required Range
         5 (33)
         5 (16)
         5 (17)
        10 (59)
RELATIVE HUMIDITY f%)

b
9/85
10/85
11/85
12/85
15
31
30
17
Protocol-required
Protocol-required
52.
50.
35.
19.
range =
range =
2 ± 9
6 ± 11
8 ± 11
2 ± 10
69-75°
35-65%
.6
.9
.6
.2
F
39-65
30-80
12-58
8-42

15
27
16
2

(100)
(87)
(53)
(12)

C.  Experimental Design

    During the second week of quarantine, animals were examined by the
    Staff Veterinarian and were found to be acceptable for use on
    study.  The animals were randomized on the basis of body weights
    into four groups of 30 animals per sex.  Ten male and ten female
    rats were selected for baseline hematology and serum chemistry
    determinations.  Three additional rats/sex/dose were placed on
    test for neuropathology studies.  This phase of the study was
    subsequently terminated in Test Week 2 following Sponsor request,
    and the animals were discarded.  The following dose levels were
    selected by the Sponsor on the basis of preliminary studies which
    included a two-week range-f inding/exploratory test (Appendix A),
    and were administered once daily by gavage for at least 13
    consecutive weeks.

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                                               Study No. 5221.06
Treatment     Dose Level    Number of Animals   Dosage Formulation
   Group .     (TO/kq/day)     Male    Female    	(mg/ml)	

     1             0           30         30              0
     2            50           30         30             10
     3           175           30         30             35
     4           600           30         30            120
     5   Baseline Clin.  Path.   10         10
The test chemical was diluted  in corn oil on a weekly basis to
achieve  the above concentrations which allowed for a dosing volume
of. 5 ml/kg.  The concentration of o-cresol in corn oil was
analyzed from dosage forms used during Test Weeks 1, 2, 4, 8 and
13  by ENSECO Inc., Cambridge,  MA.  Additionally, American Biogen-
ics Corporation, Decatur, IL tested the stability of o-cresol
dosage forms following a 14-day holding period.  Finally, several
samples  were subsequently sent to both ENSECO Inc. and American
Bicgenics Corporation for confirmatory analyses.  Analytical
chemistry methodology can be found in Appendix B.

All rats on test received a unique test animal number which
appeared as an ear tag.  A cage card appeared on the front of each
cage and contained the following information:  study number,
animal number, test article name,•treatment group name or number,
room number, dose level, strain, sex, receipt date and start date,
The cage cards were color-coded as a function of treatmant group
and sex,

The test article or vehicle (corn oil)  was orally administered
once daily for at least 13 consecutive weeks commencing on
16  September 1985.  Animals were dosed up to the day prior to
routine necropsy in either Test Week 7 (interim kill) or 14
(terminal kill).  The gavage procedure was accomplished by the use
of  a rigid oral feeding needle.

Non-fasted body weights were recorded on Test Day 1 and weekly
thereafter.  Individual food consumption data were collected on a
weekly basis.  Moribundity/mortality checks were routinely
performed twice daily (once in the morning and once in the
afternoon), and moribund animals were killed and necropsied.  The
test animals were examined once weekly for clinical signs of
toxicity.

Ophthalmology examinations were performed during the quarantine
period and in Test Week 13 by Dr. Nancy Brcmberg, Diplomate,
American College of Veterinary Ophthalmologists.  This procedure

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                                               Study No. 5221.06
 was done by indirect cphthalnosoqpy, and only animals which were
 free of visible lesions were considered for test aniitial selection.

 Blood samples were collected from  10 rats per sex which were
 designated for  baseline clinical pathology determinations, 10 rats
 per sex per dose sacrificed during Test Week 7, and 10 rats per
 sex per dose sacrificed at study termination (Test Week 14},
 Blood was obtained from the retro-orbial sinus following an
 approximate 16-18 hour fasting period.  The following hematology
 and clinical chemistry tests were  performed;

 Hematploqy
 Hemoglobin
 Hematocrit
 Erythrocyte count
 Total and differential leukocyte count
 Erothrombin time (FT)*
 Activated partial thrombcplastin time (AFTT)*
 Ifeticulocyte count

 Clinical Chemistry
 Sodium*
 Qiloride*
 Potassium*
 Calcium*
 C02
 SGPI
 SG0T
 Glucose
 BUN
 Direct and total bilirubin
 Alkaline Hiosphatase
 Total cholesterol
 Albumin
 Globulin (calculated)
 Total protein
A/G  ratio (calculated)
 Creatinine
Hiosphorus
*  Test not performed at
   baseline interval due
   to technician error.

Urine specimens were obtained from 10 rats per sex per dose
sacrificed during Test Week 7 and from 10 rats per sex per dose
sacrificed at study termination.  The urine specimens were
collected from metabolism pans into gauze-filtered urinalysis cups

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                                                Study No.  5221.06
 during the overnight fasting period.   The following urinalysis
 parameters were assessed:

 Urinalysis
 Appearance
 Volume
 Color
 Specific gravity
 PH
 Protein
 Glucose
 Ketones
 Bilirubin
 Urobilinogen
 Microscopic examination

 Clinical pathology methodology is  contained  in Appendix C.

 Complete gross necropsy examinations were performed on all rats
 found dead during the study and those  killed at the interim and
 terminal sacrifices.   Rats  assigned to the interim  sacrifice
 (identified at study onset)  were killed  in random order over a
 consecutive two-day period.   At the terminal sacrifice, all
 surviving rats were killed  in random order over a consecutive
 three-day period.  All rats were anesthetized with  003 and
 exsanguinated by bleeding from the posterior vena cava.

 Animals were fasted overnight prior to necropsy.  The necropsy
 procedure included a  thorough and  systematic examination and
 dissection of the  animal viscera and carcass, and collection and
 fixation of the following tissues/organs in  10% neutral buffered
 formalin:

All gross lesions                   Corpus and cervix uteri
 Brain (3 levels)      '              Spleen
Eye                             !    Bone (with narrow)
Pituitary                          Skeletal inuscle
Salivary gland                     Lymph node (mandibular)
Heart                              Spinal cord
Thymus                              Mammary gland
Thyroid  (with parathyroid)          Aorta
Lungs (with mainstem bronchi)       Sciatic nerve
Trachea                  .           Liver
Esophagus                           Kidneys
Stomach                             Urinary bladder
Small and large intestine           Testes
Adrenals                            Prostate
Pancreas                            Ovaries

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                                                        Study No. 5221.06
         All of the above tissues for all control and high and mid dose
         animals were submitted for histopathologic examination.
         Histopathologic examination of the mid dose animals was performed
         due to the high mortality rate in the high dose group.

         During terminal sacrifice, in addition 'to terminal body weight,
         the heart, liver, spleen, brain, kidneys (individually), gonads
         (individually), adrenals and thyroid/parathyroid were weighed.


     D.  Statistical Analyses:

         Body weight, food consumption, clinical chemistry, hematology and
         organ weight data were analyzed by one-way, by sex, Analysis of
         Variance tests with Dunnett's t test employed if a significant
         F ratio was found (p < 0,05).  Individual animal data can be found
         in Appendix D.
IV.  RESULTS;

     A.  Analyses and Stability of Dosage Form Preparations

         o-Cresol in corn oil was found to be stable for at least 14 days
         at the concentrations tested.  Additionally, the analyses of the
         dosage form preparations used during Test Weeks 1, 2,  4, 8 and 13
         indicated that target concentrations were generally within an
         acceptable range.  At the 120 rag/ml target concentration, some of
         the samples were assayed at levels up to 28% higher than expected.
         When 16 additional samples were subsequently sent to both American
         Biogenics Corporation and ENSECQ Inc. for confirmatory analyses,
         significant witMn-sample/between laboratories variability was
         observed.  For example, sample C0658A85 with a target  concentrat-
         ion of 120 mg/ml assayed at 135.1 rag/ml, 12.6% over target, by
         American Biogenics Corporation.  ENSECO Inc., however, assayed
         this sample at 118.5 mg/ml or 1.2% under target.   In those few
         cases where a sample was outside of 10% of the intended concentra-
         tion, the assayed'value by the other laboratory was always within
         range or outside of range but in the other direction (Tables
         la-lc).


     B.  Mortality/Clinical Observations

         Nineteen females and nine males at the 600 mg/kg/day dose level
         died during the three month treatment period (Tables 2 and 3).
         Postdosing observations revealed signs of central nervous system
         (CNS)  depression in male and female rats at the 600 mg/kg/day dose
         level.   Surviving and nonsurviving high dose animals became

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                                                   Study No. 5221.06
     lethargic and experienced tremors within 15-30 minutes of dosing.
     Biis phase was followed by a comatose state and convulsions in the
     most severe cases.  Dyspnea was also observed in high dose rats on
     occasion.

     Approximately one hour  after dosing, the surviving animals
     "recovered" and appeared  normal.  As shown below, the signs of CNS
     depression were most frequently observed during the first four to
     five weeks of the study and again during weeks 9 and 11:
       Incidence of Significant Clinical Signs in High Dose Ratsa

                                                      OCMA.
M
M
                                                    M
1
2
3
4
5
9
10
11
13/30
19/28
10/26
9/24
12/24
11/13
1/12
8/12
30/30
24/28
16/24
10/18
14/18
3/6
-
5/6
9/30
9/28
4/26
— '
6/24
6/13
1/12
3/12
17/30
16/28
7/24
-
13/18
3/6
-
1/6
6/30
4/28
2/26
_
-
2/13
-
2/12
6/30
6/28
3/24
-
_
4/6
-
1/6
            Number of animals exhibiting sign/number alive at
            beginning of indicated week.
            Only those weeks during which time relevant signs
            were observed are presented.
    High dose animals also became increasingly more difficult to dose
    as the study progressed.  The animals would contort their bodies
    and attempt to resist the gavaging procedure.

    One mid dose female demonstrated tremors and became comatose on
    day 23 of the study,  toother female from this group exhibited
    lethargy and tremors on, day 27 of the study.  These signs were not
    seen at any other time for this dose group nor at the low dose
    level.  No other significant clinical signs were observed for
    o-cresol-treated rats.
C,  Body weight

    Statistically significant (p < 0.05)  reductions in body weight
    were seen for males at the high dose level (600 mg/kg/day)  during
    weeks 2 through 10, and for those males receiving 175 mg/kg/day
    during week 2 only.  Body weights of females at those doses were

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                                                   Study No. 5221.06
     unaffected by treatment.   Only low dose females  (50 mg/kg/day)
     during weeks 6,  and 8 through 14  showed significantly reduced body
     weights,  as cxanpared to controls.

     Reductions in body weight gain were seen for males administered
     175  and 600 mg/kg/day.  The weight gains of the high dose males
     were noted to be significantly lower than the controls durmg
     weeks 1 through  9.   A 30% reduction in  weight gain was evident
     following one week of treatment, however this reduction lessened
     as a function of time and was only about 10% by study termination.
     Sporadic  significant weight gains were  also observed for the
     175  mg/kg/day dose group  males for weeks l (decrease), and 10 and
     11 (increases),  as compared to the controls.

     Body weight changes were  not  apparent for females at the high
     dose.  Low dose  females showed a slightly greater rate of weight
     gain than control  animals which was noted to be statistically
     significant at weeks 5, and 7 through 13.  This was not seen for
    mid  or high dose females  and was not considered biologically
     significant.   Body weight for low and mid dose males were
    unaffected by o-cresol  (Tables  4-7).
D,  Food Consumption

    Slight decreases In food intake were generally seen during the
    first half of the study for males and to a lesser extent for
    females at the high dose level.  Significantly (p < 0.05) lower
    than control mean food consumption values were noted for the high
    dose males during weeks 1 through 6, and for the high dose females
    during week 1.  Sporadic increases and decreases were seen at the
    other dose levels but were not considered biologically significant
    (Tables 8 and 9).
S.  Clinical Pathology

    Clinical chemistry, hematology and urinalyses parameters did not
    appear to be affected by o-cresol treatment.  Sporadic increases
    and decreases were seen which were not considered biologically
    significant (Tables 10-17).
F.  Ophthalmology

    The Ophthalmology Report is contained in Appendix E.  Treatment-r-
    elated ophthalmic lesions were not seen for rats receiving
    o-cresol.

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                                                          Study No. 5221.06
        G.   Organ Weights
            Organ weights did not appear to be affected by o-eresol treatment.
            Relative left and right kidney weights of the high dose sales were
            noted to be slightly but not significantly elevated, as compared
            to the  control group values.  The higher relative kidney weights
            in this group appear to be a reflection of the slightly lower
            terminal body weights of the high dose animals,  other sporadic
            increases and decreases in organ weights were seen which were not
            considered  biologically significant  (Tables 18-21).


       H.   Pathology

            The Pathology Report is shown in Appendix F,  Treatment-related
            gross and histomorphologic lesions were not in evidence.  Although
            28 deaths occurred among the high dose animals, the cause of death
            was not determined from pathologic evaluations.  lung lesions
            including congestion and edema were in evidence for many of these
            animals.  They were, however, not considered a direct effect of
            o-cresol and may have been associated with terminal stress.  In
            addition, oil droplets found in the lungs of these aniroals may
            have been due to aspiration of o-cresol/corn oil during a convuls-
            ive seizure.  Additionally, none of the surviving high dose
            animals demonstrated histatnorphologic changes of the lungs.


   V.  DISCUSSION;

       This study  evaluated the oral toxicity of ortho-eresol in Sprague
Dawley rats when administered for 13 weeks by gavage.   Nineteen females and
nine males  at the high dose died during the study.   Clinically, surviving and
nonsurviving high dose anfooals showed QB depression and were generally
lethargic/ataxic with tremors and/or convulsions.  These observations were
reversible  for surviving animals as they generally appeared normal within one
hour after  dosing.  High dose males but not females also showed an approxim-
ate 10% reduction in body weight gained by the end of the 13-week treatment
period.  With the exception of CMS depression observed for two mid dose
animals on  one occasion, no other clinical effects of o-cresol were in
evidence.

       Clinical chemistry,  hematology,  urinalyses,  and organ weight measurem-
ents failed to detect treatment-related changes.  In addition,  ophthalmology
and pathology examinations did not identify o-cresol target organs.  Thus,
the cause of death for high dose animals was not established.  The central
nervous system appears clinically to be affected by o-cresol treatment.

       In summary, the biological effects of o-cresol were generally restric-
ted to the high dose level under the conditions of the present study.

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                                                          Study No. 5221.06


Treatment-related central nervous system depression was apparent, and
probably contributed to the death of these animals.


  VI.  HSRSCMMgL!

       L. T, Mulligan, Jti.D. served as Study Director, and was responsible
for the overall conduct of the study.  Barry S. Levine, D.Sc., Diplomats,
American Board of Toxicology, was Study lexicologist and was responsible for
the in-life portion of the study and for clinical pathology evaluations.
Diana S. Copeland, DVM, Diplomats, American College of Veterinary Patholcgis-
ts, was responsible for gross necropsies and histopathologic evaluations.
John Miller, DVM, was responsible for laboratory animal care.  Harry J.
Baulin, M.S., served as Study Chemist, and provided dosage formulations and
analytical chemistry services.  Nona S. Karten, M.A., was responsible for the
Quality Assurance Program.  Mite Schulz, B.S., and Brian Makle, B.S., were
responsible for the collection of in-life test animal data.


VII.  ARCHIVES;

       The raw data and final report are archived at Microbiological Associa-
tes Inc., 5221 River Road, Bethesda, MD 20816 with the following exceptions.
Pathology specimens including wet tissues, blocks and slides and original
necropsy forms are temporarily archived at Pathology Associates, Inc., 10075
Tyler Place, Hyatt Park II, Ijamsville, MD  21754 and will be transferred to
the MBA. Archives upon Sponsor approval of the final report.
                                     10

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                                                                 Study 5221,06
                                   TABLE la

            SUBCHRONIC TOXrCITY OF ORIHO-CPISOL IN SERAGUE DMCEY EMS
                    CDNCSNTRKTION OF ORIBD-CRESOL IN CORN OIL  (ing/tal)



                             STABILITY ANALYSES3
Sample
Number
C0162A85
C0164A85
C0744A85
Date
Mixed
9/15/85
9/15/85
9/15/85
Target
Cone, (ma/ml)
10
120
120
Concentration (mar/ml)
Zero Day 14-Day
10,28b 10.15
127.3 • 123.4
126.2 117.3
Percent
Difference*
-1.3
-3.1
-7.1
*Percent Difference = 14-Day Value minus Zero DayJ/alue   x 100
                                Zero Day Value

aAnalyses performed in duplicate by American Biogenics Corporation unless
noted otherwise.

^Analyses performed in triplicate.
                                     -11

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                                                                                    Study 5221.06
to
                                                     TJiBLB li)

                            SUBCHRDNTG TOJOCTZY OF ORTHO-CRESOL IN SPRM3JE Dmi£¥
                                               OF ORTHO-CRESOL IN OOKM OIL

Target
Concentration
(m/ml)
0
10
35
120


1
ND
9.1
37.8
141.5
FORMULATION AWALKSES3
2test Week
24 8 13
ND WD ND ND
5.5 10.5 9.8 10.5
39.2 40.2 37. 4 34.2.
143.3 153.1 128.6 136.8
       aAnaIyses performed by EKSEQO Inc.  (formerly EROO), Cambridge, MA unless otherwise noted.

       ND - Not detected above the minimm reporting limit of 1.0 mg/ml.

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                                                                             Study Wo.  5221.06
                                              TABLE Ic

                     SOBCHSOMTC TOXICHY OF QFTHO-ORESOL IN SPRM3JE DWLEY
                      O3NFIRMMDI& MM.YSES OF OKTHO-CRESOL JN CORN OIL
                                                     Merican
                      Target Concentration      Biogenics Corporation            JEWSECO Inc.
Sample Mmter         _ (ing/ml) _      Assay Values (mg/ml)a      Assayed Values fmg/ml ) a

  C0161M5                     00                            ND
  C0502M5                     0                          0                            ND
  C05B7M5                     0                          0                    '        ND
  C0617A85                     00                            ND
  C0185M5                    35                         38.0                         30.3
  C0256M5                    35                         37. 8                         32.3        ,
  C0834M5                    35                         38.9                         30.4
  C0974AB5                    35                         36. sP                        30.0
  C0164AB5                   120                        127.3                        119.8 ,
  CQ186A85                   120                        130.6                        122.2
  C0257M5                   120                        131.6                        131.2
  C0505M5                   120                        126. 6b                       223.0
  C0627A85                   120                        130.4                        107.2
  C0658A85                   120                        135.1                        118.5
  C0744A85                   120                        126.2                        112.7
  O0957A85                   120                        129.2                        114.9


  aMean of duplicate assays unless otherwise noted.

  %ean of triplicate assays.

  ND = Not detected above the minimm reporting limit of 0.1 ng/ml.

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                                                                                Study No. 5221.06
                                              TAHIE 2

                                suBCHRONie TOXICITY OF ORTHO-CRESOL
                                       IN SPRAGUE DAWLEY RMS

                                      Male Mortality Summary*
Test
Week
1
2
3
4
5
6
7
8b
9
10
11
12
13
14
0
mq/kq/day
30
30
30
30
30
30
30
20
20
20
20
20
20
20
50
mcr/kcr/dav
30
30
30
30
30
30
30
20
20
20
20
20
20
20
175
m/kq/dav
30
30
30
30
30
30
30
20
20
20
20
20
20
20
600
mq/ker/day
28
26
24
24
24
23
22
13
13
12
12
12
12
12
aSurvivors (n=30 through Test Week 1,  and 20 thereafter).

b!0 rats/sex/dose were used for the scheduled interim kill during Test Week 7.   Only 9  of the 10
initially identified interim-kill males at the 600 mg/Joy dose level were available.

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                                                                                 Study Ho. 5221.06
                                               TABLE 3

                                 SUBCHROHTC TOXfCmf OF ORTHO-CRESOL
                                        IN  SPRAGUE  DAWLEY  RATS
                                      Female Mortality Summary
                                                              a
Test
Week
1
2
3
4
5
6
7
8b
9
10
11
12
13
14
0
msAkg/day
30
30
30
30
30
30
30
20
20
20
20
20
20
20
50
mg/kg/d BY
30
30
30
30
30
30
30
20
20
20
20
20
20
20
175
mg/kg/day
30
30
30
30
30
30
30
20
20
20
20
» 20
20
20
600
mg/kq/day
28
25
18
18
17
13
13
6
6
6
6
6
5
4
BSurvivors
-------
                                                                                     Study No. 5221.06
                                           TABLE 4
                  SUBCHRONJC  TOXICITY OF CSTHO-CSESOL IH SPRAGUE OAULEY RATS
                                  HALE ICOY WEIGHT DATA (g)

    TEST
    WEEK         0 mg/kg/day        50 mg/kg/day        175 ing/kg/day       600  mg/kg/day

      1         223 *    10C 30)     222 *   10( 30)     219 *   10( 30)     221 *   SC 30)

      2         2B2 ±    13( 30)     283 ±   15< 30)     270 t   16< 30)*    264 t   13C 28}*

      3         324 t    17( 30)     328 ±   16C 30)     319 t   Z2( 30)     304 t   16< 26)*

      4         337 *    20< 30)     343 t  . 19< 30)     333 t   29< 30)     313 t   17( 25}*

      5         378 ±    23( 30)     384 t   22( 30)     377 t   26( 30>     348 t   21( 24)*

      6         397 ±    24< 30)     406 *   24< 30)     397 t   39{ 30)     360 t   31( 24)*

      7         430  t    27C 30)     439 ±   24( 30)     434 t   34( 30)     39! i   26< 23)*

      8         450  *    28C 30)     451 ±   40< 30)     456 i   37C 30)     406 t   28< 23)*

      9         476  t   33< 20)     483 t   33( 20)     475  t   38( 20)     436 ±   3S( 13)*

    10         493  i   34< 20)     499 t   38( 20)     495  *   43< 20)     441 ±   49< 13)*

    11         488  t   33{ 20)     498 t   42< 20)     518  ±   47<  20)     457 t    51( 12)

    12         511 t   36C 20)     525 t   39C  20)     538  i   49C 20)     483 *    46{ 12)

    13         530 *   37< 20)     542 t   43<  20)     552  t   52<  20)     498 *   45C 12)

    14        547 ±   40( 20)     557 *    46(  20)    566  ±   52(  20)     514 ±   45C 12)


     Weights taken on lest Day 1  prior  to  dosing.

* •- Statistically significant difference  froai control group
     using ANOVA and  Dunnett's T-Test  (P<=0.05).

     Results presented as mean ±  standard  deviation ( M )
                                       16

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                                                                                    Study No.  5221.06
                                           TABLE 5
                  SUBCHROHIC  TQXICm OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                                HALE BODY WEIGHT GA5H DATA (g)
TEST
UEE*C 0 tng/kg/day
1 59 t
2 102 ±
'3 114 t
4 155 *
5 174 i
6 207 *
7 227 *
8 253 t
9 270 1
10 266 t
11 2Sfl i
12 308 1
13 324 *
13(
17C
19C
23(
24 (
27<
27C
33(
34{
34<
38(
38(
41(
30}
30}
30}
30)
30}
30}
30}
20}
20}
20)
20)
20}
20)
50 mg/kg/day
60 i
106 *
121 t
162 ±
184 1
217 t
229 t
260 ±
277 *
276 t
303 ±
319 *
334 ±
IK
UK
14(
19C
20C
2K
37<
28(
34(
38{
35 (
40(
43(
30}
30)
30)
30)
30}
30}
30}
20)
20}
20)
20)
20}
20)
175 mg/kg/day
50 t
100 i
114 i
157 i
178 4
214 i
237 *
257 i
277 i
300 t
320 *
334 ±
348 J
8<
«C
21 C
20<
33 <
29C
32(
34C
40C
43(
46{
49<
49(
30)*
30)
30)
30)
30)
30)
30}
20}
20)
20)*
20}*
20}
20)
600 mg/kg/day
42 *
82 i
91 t
126 ±
137 t
168 t
183 ±
212 i
216 *
232 *
258 t
273 t
289 t
8( 28)
10( 26)
12( 25)
17( 24)
29( 24}
23 ( 23)
25 C 23)
31C 13)
47( 13}
49{ 12}
42( 12)
41( 12)
41 ( 12}
*
*
*
*
*
*
*
*
*




* -• Statistically significant difference from cantrsl  group
     using AMOVA and Dunnett's T-Test {P<=0.05).

     Results presented as mean i standard deviation ( H )
                                           17

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                                                                                     Study No.  5221.06
                                            TABLE 6
                  SU8CHRQNIC TOXICITY OF ORTHO-CRESOL  IN SPRAGUE DAULEY RATS
                                  FEMALE BODY y£lGHT DATA (g)
TEST
WEEK
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0 mg/kg/day
155 ±
175 ±
198 i
201 t
220 *
222 ±
237 i
242 i
250 *
255 *
262 ±
267 t
269 t
' 274 t
8( 30)
10C 30)
12( 30)
12( 30)
14( 30)
14( 30)
15( 30)
15( 30)
15( 20)
16C 20)
14C 20)
1B( 20)
18( 20)
17( 20)
50
158
180
202
207
227
233
247
255
270
276
285
293
295
303
nig/kg/day
* 7( 30)
i 9( 30)
± 13( 30)
i . 13( 10)
± 15( 30)
± 17( 29)*
± 18C 30)
t 19( 30}*
t 22( 20)*
± 23C 20)*
± 25( 20)*
* 27C 20)*
± 30( 20)*
i 29{ 20)*
175
157 ±
179 i
201 ±
204 t
221 ±
229 t
241 4
245 t
257 ±
264 i
267 ±
276 ±
281 *
285 ±
ms/ki/day
9( 29)
13( 30)
15( 30)
16C 30)
2K 30)
19( 30)
20C 30)
22( 30)
21C 20)
24( 20)
24{ 20)
26 C 20)
25( 20)
24C 20)
600
154 ±
171 ±
192 *
196 t
215 t
220 ±
229 i
232 ±
239 t
248 i
256 *
262 t
270 t
273 t
ing/kg/day
IK 30)
12( 28)
14( 25)
14( 21)
18( 18)
16C 18)
15C 13)
17( 13)
23( 6)
20C 6)
19( 6)
20 ( 6)
21C 6)
19( 6)
     Weights taken on Test Day 1 prior to dosing.

* -- Statistically significant difference from control  group
     using ANOVA and Ounnett's T-Tesr (P<=0.05).

     Results presented as mean i standard deviation ( N )
                                          18

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                                                                                Study No, 5221.06
                                       TABLE  7
             SUBCHSOMIC TOXICITY OF  ORTHO-CRESOL  IN  SPRAGUE DAWLEY RATS
                          FEMALE BOOT WEIGHT  GAIN DATA  (3)
TEST
WEEK 0 mg/kg/day
1 20 s
2 43 *
3 46 t
4 64 t
5 67 i
6 82 i
7 87 *
8 97 1
9 101 ±
10 108 ±
11 113 t
12 115 i
13 120 i
5{ 30)
8( 30)
9( 30)
9( 30)
11C 30)
12C 30)
12{ 30)
15C 20)
16( 20)
15C 20)
18( 20)
18( 20)
18( 20)
50 mg/kg/day
22 i
44 ±
49 t
69 t
75 *
89 1
97 i
112 i
118 t
127 ±
135 t
137 t
144 ±
5( 30)
7( 30)
9( 30)
11< 30)
12{ 29)*
14( 30)
15{ 30)*
17{ 20)*
18( 20)*
20( 20)*
22{ 20)*
25( 20)*
24( 205»
175 mg/kg/day
22 t
44 ±
48 1
65 1
73 i
85 t
89 t
101 t
108 t
112 ±
120 *
125 ±
129 t
6( 29)
8C 29)
9( 29)
15( 29)
12( 29)
14( 29)
17C 29)
16( 19)
19C 19)
18( 19)
21( 19)
21 ( 193
21C 19)
6DO mg/kg/day
18 i
39 *
42 ±
60 ±
65 i
74 t
77 *
81 t
91 t
98 i
105 t
113 i
116 t
5C 28)
7< 25)
7( 21)
1.1 C 18)
11C 18)
12{ 13)
12{ 13)
21< 6)
18C 63
18( 6)
20( 6)
21 C 6)
20C 6)
Statistically significant difference from control group
usins ANOVA and Ounnett's T-Test (P<=0.05).

Results presented as mean i standard deviation (  N )
                                        19

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                                                                      Study Ho. 5221.06
   TEST
                                            TABLE 8
                  SU8CHRONIC  TOXICITY OF DRTHQ-CRESOL  IN SPRAGUE DAULEY RATS
                              HALE  FOOD CONSUMPTION DATA Cg/day)
WEES
1
2
3
4
5
6
7
8
9
10
11
12
13
0 mg/ki/day
23.7 ±
25. S 4
25.1 *
25.1 i
25. D t
25.8 *
22.4 i
22.0 t
15.8 i
21.71
23.5 4
23.2 1
22.1 i
2.0(
4.2C
3.6C
2.9(
2.5C
3.3C
5. 1C
3. 1C
3.7(
4.K
2.6<
2.6(
2.9C
30)
30)
30)
30}
30)
30)
30)
20)
20)
20)
20)
20)
20)
50 mg/kg/day
23. 5 t
27.2 ±
24.7 i
24,7 4
24.6 ±
23.7±
19.4 i
20.8 4
15.6 i
21.7 ±
23.0 i
21.2 4
20.8 t
1.6(
2.10
2.9(
2.4<
2.2(
3.5C
6.6(
3.2(
4.7(
2. 1C
2.3(
3.7<
4.4<
30)
30)
30)
30)
30)
30)*
30)*
20)
19)
20)
20)
20)
20)
175 mg/ki/day
22.6 t
25.7 *
23.4 4
26.3 *
24.7 i
25.7 i
23.4 *
22.3 4
24.4 *
22.9 ±
23.6 t
23.0 i
22.0 ±
2.9(
3. 1C
2.6<
2.6<
3.K
2.9{
3.9(
3.7(
4.0C
3.3<
3.2(
3.3C
4.2C
30)
30)
30)
30)
30)
30)
30)
20)
20)*
20)
20)
20)
20)
600 mg/kg/day
21.1 *
22.3 t
21.7 i
23.3 ±
22.9 s
22.1 4
19.8 ±
19.5 t
20.8 t
21.2 4'
23.3 4
23.7 i
22.3 4
2.7< 28)'
4.3C 27}<
2.4{ 24)'
2.6( 24}'
2.4C 24)'
2.5C 23)'
2.6C 23)
5.2( 13)
5.2( 13)*
6.K 13)
3.4{ 12)
3.2( 12)
3.7C 12)
* •- Statistically significant difference from control group
     using ANOVA and Dunnett's T-Test 
-------
                                                                    Study No.  5221,06
                                      TAiLE 9
             SUBCHRONIC TOXIC1TY Of QRTHQ-CRESOl IN SPRAGUE DAWLEY RATS
                       FEMALE FOCC CONSUMPTION DATA (g/day)
TEST
WEEK
1
2
3
4
5
6
7 •
8
9
10
11
12
13
0 mg/kg/day
15.5 *
17.1 *
18.1 t
16.7 t
16.5 t
16.9 *_
13.9 i
14.1 ±
14.3 ±
14.8 t
14.1 t
13.7 *
13.8 ±
1.6
6.9
6.3
2.7
3.0
3.5
2.3
1.7
2.5
3.3
2.5
1.3
1.9
(30)
(3D)
(30)
(30)
(30)
C30)
(30)
(20)
(20)
(20)
(20)
(20)
(20)
50 ms/kg/day
14.5 ±
17.0 t
16.3 t
16.5 t
16.3 i
16.3 ±
14.8 i
14.3 t
15.8 i
15. 7 i
15.1 i
14.5 i
15.3 t
3.0
3,6
2.4
3.1
3.1
2.0
6.0(
3.2
2.0
1.8
2.0
1.8
1.8
(30)
(30)
(30>
(30)
(30)
(30)
29)
(20)
(20)
(20)
(20)
(20)
(20)*
175 mg/kg/day
16.0 i
15.5 4
16.0 ±
16.2 t
16.0 i
15.8 t
13.8 ±
14.1 ±
14.3 ±
14.5 t
14.2 ±
13.8 t
14.0 t
1.8
3.8
6.0
3.6
2.7
2.3
2.5C
1.6
3.9
3.7
2.8
2.1
1.5
(30)
(30)
(30)
(30)
(30)
(30)
29)
(20)
(20)
(20)
(20)
(20)
(20)
600 mg/kg/day
13.7 ±
14.2 t
14.7 t
15.7 *
15.1 i
16.3 t
1V. 9 t
14.0 i
14.2 t
14.5 ±
14.6 ±
14.5 ±
13.1 t
1.9 (28)*
3.6 (28)
4.8 (18)
2.6 (18)
2.2 (17)
5.2 (13)
2.1 (13)
2.6 (6)
1.6 (6)
1.9 (6)
1.8 (6)
1.4 (6)
2.0 (6)
Statistically significant difference from control  group
using ANOVA and Dunnett's T-Test (P<=0,05).

Results presented as mean 4 standard deviation  ( H )
                                               21

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                                                                                   Study No. 5221.06
  Parameter
                            TABLE 10
  SUBCHROHIC TQXICITY OF ORTHO-CRESOl 1H SPRAGUE DAWLEf RATS
                    MALE HEMATOLOGr VALUES •
                      [Interim Sacrifice]

   0 mg/kg/day        50 mg/kg/day        175  mg/kg/day      600 mg/kg/day

7.87 * 0.36< 10}    8.10 i 0.56C  10)    7.94 ± 0.29C  10)     7.75 ± 0.51C  9)


15.6 1  0.5C 10}    15.7 i  0.9C  10}    15.4 t  0.5C  10}     15.3 ±  0.5<  9)


43.5 ±  2.2< 10)    44.2 i  2.9<  10)    44.4 t  1.5C  105     43.8 ±  2.0C  9)
     RBC
(x 10'
      HCB
    (g/dl)

     HCT
      PT        11.8  *   0.6C  10)     11.7 i  1.1C 10)    11.9 * '0.8C  9)    11.4 *  0.6C  9)
    (sec.)

    APTT        30.7  *   2.0C  10)     33.9 i  3.2C 10)    32.9 i  2.5C  9)    32.6 t  2.3C  9)
    (sec.)

    RETIC         0.9  ±   0.3(  10)     0.7 ±  0.4( 10)     0.8 ±  0.5( 10)     O.B i  0.6C  9)
   (%  rbc)
    Results presented as mean ± standard deviation < N )
                                        22

-------
                                                                                   Study Mo. 5221.06
                                      TABLE 10 (continued)
                  SUBCHROM1C TOXIC1TY OF QRTHO-CRESOL IK SPRACUE  DAULEY  RATS
                                    MALE HEMATQLOGY VALUES
                                      [Interim Sacrifice]

  Parameter        0 mg/kg/day        50 tng/kg/day       175 ing/kg/day       600 mg/kg/day
     WC        16.7 ±  3.2(  103
Cx IQ'
                                    14.6 t  3.6(  10)     14.2 ±  2.71  10}    14.8 ±  2.3(  9}
     SEGS        1.4 t  0.8(103     1 .4 i  1.0(10)      1.6*  0.8(10)      1.8 1  0.8(  9}
                                     0.1  i   0.2(  10)     0.0 t  0,0( 10}     0.0 *  O.U  9)
                                    12.6  ±  3.0(  10)    12.0 * "2.5C 10)    12.5 4  2.4<  9)
(x
    BANDS        0.0 4  O.K 10)
(x 1QA3/m*3)

    LYMPHS      15.0 1  2.9( 10)
(x 10*3/mmT3)
(x
     MONO        0.2 i  0.2C  10)     0.3 t   0.2(  10)      0.3 4  0.3<  10)     0.3 *  0.3C  9)
                 0.1  4  0.1(  10)      0.2  4   0.3(  10>     0.1 *  0.2( 10)     0.1 i  0.2C  9)
     EOS
     Results presented as mem t  standard deviation  ( N  )
                                          23

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                                                                                   Study No.  5ZZ1.0A
                                          TABLE 11
                  SUBCHSONIC  TCXICITY OF ORTHO-CRESQL 1H SPRAGUE DAWLEY RATS
                                   MALE HEMATOLOGY VALUES
                                     [Terminal Sacrifice]

  Parameter        0 mg/kg/day        50 mg/kg/day        175 Mg/kg/day       600 mg/kg/day

     RBC        8.62 ±  0.27(  10)    8.55 i 0.41( 10)    8.57 ±.0.47( 10)    B.5B i 0.61C  6>
IK 10*6/mm"3)

      HGB        15.2 *  0.4(  10)    15.2 ±  0.4( 10)    15.4 t  0.5C 10)    15.4 i  0.5<  6)
    Cg/dl)

     HCT        43.3±  1.4(  10)    42.9*  1 .9( 10)    44,1 s  1.7C 10)    43.91  1.8C  65
      PT         10.7 t  2.1< 10)    11.1 t  1.6C 10)    12.2 ± "0.7< 10)    10.71  3.5(  6)
    (sec.)

    APTT       34.4 ±  4.6( 10)    33.8 ±  2.5C 10)    32.9 i  5,6( 10)    30.1 t  9.8(  6)
    (sec.)

    RiTIC        0,91  0.4(10)     1.1 ±" 0.9(10)     1.5 ±  0.9(10)     1.3 ±  1.4(  6)
  (%  rbc)
    Results presented as mean t standard deviation <  N  )
                                         24

-------
                                                                           Study No.  5221,06
                                     TABLE 11 (continued)
                  SUBCHROHIC TCX1CITY OF CRTHO-CRESOL IN SPRAGUE DAWLEY RATS
                                    HALE HEHATOIOGY VALUES
                                     [Terminal Sacrifice]

  Parameter       0 rog/lcg/day        50 mg/kg/day        175 mg/kg/day       600 mg/kg/day

     UBC        H.3 ±  2.1C 10)    12.6 *  2.6C 10}    14.0 *  2.3< 103    14.2 ±  3.4(   6)
(x 10"3/imr3>

     SEGS        2.8 i  -2.0C 10}     2.2 ±  1.2C 10)     2.5 t  0.9< 10)     2.1  i  1.4(   6)
(x 10*3/rmr"3)

    BANDS        0.1 i  O.H 10)     0.1 i  O.K 10)     0.0 ±  0.1( 10)     0.1  *  0.1(   6)
(x 10A3/rra*3)

    LYMPHS      11.1 i  1.7( 103     9.7 t  2.2( 10)    11.0*  2.5( 10)    11.4  t  3.5<   6)
(x 1tr3/nnT3)

     HWO        0.2 *  0.2< 10)     0.5 i  0.4( 10)     0.3 ±  0.2( 10)     0.5  i  0.4<   65
(x 10*3/11111*3}

     IDS         0.1 ±  O.K 10)     0.0 i  O.K 10)     0.1 i  0.1C 10)     0.1  ±  0.1<   6)
(x lO'S
     Results presented as mean * standard deviation (  N )
                                               25

-------
                                                                                    Study No.  5221.06
                                           TABLE 12
                  SUBCHRONIC TOXICITY OF QRTHO-CRESOL IM SPRAGUE BAWLS? SATS
                                   FEMALE HEHATOLOGT VALUES,
                                      Unterim Sacrifice]

  Parameter        0 mg/kg/etey        50 mg/kg/day        175 mg/kg/day       600 mg/kg/day
                                                                                   \

     RIC        7,98 i 0.20C 10)    7.89 * 0.36<  9)    7.55 ± 0.47t 10)    7.71  ± 0.33(   fi)
(x 10*6/11111*3)

      HG8       15.6 i  0.4C 10)    15.7 *  0.8C  9)    15.3 *  0,6( 10)    15.3  *  0.3(   6)
    (S/dl)

     HCT        44". 2 ±  1.3(10)    43.6 ±  2.41  9)    41.6 t  2.6( 10)    43.1s  1.3(   6)
      PT        11.0 ±  0.5C 10)    10.7 4  0.6C 10)    10.9 ± -1.1(  10)    11.6 ±   1.1C  6)
    (sec.)

     APTT       35.3 t  5.8C 10)    33.9 i  4.0C 10)    34.0 S  4.9<  10)    36.4 t   4.3(  6)
    Csec.)

    R6T1C        0.8 t  0.7< 10)     0.7 i  O.SC 10)     0.6 ±  0.4<  1C)     1.9 ±   1.3{  6)*
   <.% rbc)
* -- Statistically significint difference from control  group
     using AKOVA and Dunnett's T-Test (P<=0.05).

     Results presented as mean t standard deviation ( N )
                                            26

-------
                                                                         Study No. 5221.06
                                     Table 12 (continued)
                  SUBCHROMIC TOXtCITY OF QRTHQ-CRESQl IN SPRAGUE DAULEY RATS
                                   FEMALE HEMATOLOGY VALUES
                                      [Interim Saerifice]
  Parameter       0 mg/kg/day        50 mg/kg/day        175 mg/ki/day       600 mg/kg/day

     USC        10.9*  2.4(10}    12.7 t  4.7(9}     12. It   1.9<10}    13.7*  3.6 {63
(X 10A3/mm"3}

     SEGS        1.0 t  0.4 (105     1.5 i  1.4  (9)      1.4 i   D.9  (10)     1.8 ±  1.1 £6}


    BANDS        0.0 i  0.1 (105     0.0 i  0.0  <9)      0.0 ±   0.1  (10)     0.0 t  0.0 (65
(x 1
    LYMPHS       9.5 t  2.1(10)    10.9*   4.0(9)     10.4 i  1.6(10}    11.71  3.7(6)
Cx 10*3/nm*3)

     MONO        0.2 ±  0.1  (10)     0.3  t   0.3  (9)     0.2 i  0,2 CIO)     0.2 ±  0.2 (6)
(x KTS/flm^)

     EOS         0.1 ±  0.1  (10)     0.1  t   0.1  (9)     0.1 i  0.1 (10)     0.0 i  0.1 (6)
(x 1
     Results presented as  mean ±  standard deviation ( K J
                                          27 _

-------
                                                                          Study Ho. 5221.06
  Parameter

     RSC
                                       TABLE 13
              SUBCHRQNIC TOXICITY OF ORTHQ-CRESQL IN SPRAGUE  DftULEY  RATS
                               FEMALE HEHATOLOGy VALUES
                                 ITerainal Sacrifice]

              0 mg/kg/day        50 mg/kg/day        175  mg/kg/day        600 mg/kg/day

            8.43 ± 0.43 (10)    8.36 ± 0.27 (10)    8.31  t  0.43  (103    8.38 t 0.59 (4)


            15.8 *  0.7 (10)    15,8 t  0.5 (10)    15.4  ±  0.7  (10)    15.6 ±  0.5 (4)


            44.0 *  2.5 (105    44.2 i  1.3 (10)    43.3  i  2.0  (10)    44.6 t  1.8 (4)
(x
      HGB
    (9/dl)

     HCT
      PT         10.9  *   0.7  (10)     11.0  ±   1.2  (10)     10.6 ±  -2.0 (10>    10.7 t  0.4 (4)
    (sec.)
 APTT
(sec.)
                32.9  i   6.1  (10)     33.2  1  3.4  <10)    36.1 1  7.8 (10)    36.4 *  9.0 <4)
    RET1C         1.2  *   0.8  (10)     0.8 1  0.4 (10)     1.3 *  0.7 (10)     1.4 i  0.4 (4)
   (X  rbc)
    Results presented as mean i standard deviation ( N )
                                            28

-------
                                                                                   Study Mo, 5221.06
                                     TABLE 13 (continued)
                  SUBCHRQNIC TCXIC1TY OF ORTHO-CSESOL  IN SPRAGUE DAWLEY RATS
                                   FEMALE KEMATCLQGY VALUES
                                     [Terminal  Sacrifice]

  Parameter        0 mg/kg/day        50 ing/kg/day        175 mg/k§/day       600 mi/kg/day

     UBC        10.5 t  2.3( 10)     9.6 i  2.4(  10)     8.9 i  1.5( 10)    10.9 i  0.8(-  4)
(x 10"3/mm*3)
     SEGS
(x
    BANDS
1.9 *  1.5C 10)     1.4 t  0.5(  10)      1.4 i  O.S( 10)     2.2 i  1.7(  4)
0.1 ±  O.K 10)     0.1  ±  O.K  10)      0.0 i  O.K 10)     0.0 t  O.OC  4)
    LYMPHS
8.1 t  1.9( 10)     7.9 t  2.0(  10)      7.1 t* 1.S( 10)     8.7 t  1.9(  4)
(x
     HONO        0.3 ±  0.2( 10)     0.2 t   0.2(  10}     0.2 ±  O.K 10)     0.0 *  O.K  4)*

* •• Statistically significant difference  from control group
     using ANOVA and Dunnett'S T-Test  (P«0.05).

     Results presented as mean ±  standard  deviation  ( H >
                                          29

-------
                                                                                       Study Ho.  5221.06
                                              TABLE  14
                      SUBCHRONIC TOXICITY OF ORTHO-CiESOL  IN SPRAGUE UAULEY RATS
                                    MALi CLINICAL CHEMISTRY VALUES
                                          [Interim Sacrifice]
  Parameter       0  mg/kg/day         50 mg/kg/day          175 nig/kg/day         600 mg/kg/day

     GLU      170.4  *   35. 4<  10)     182.9 t  47. 2C 10)    215.8 ±  48. 9< 10)    209.9 I  70. 2C   9}
   
   SCOT         77 *     9( 10)       72 t     9< 10)       73 ±     5( 10)       79 t     11(  9)
   T PRO       6.7 1   0.51 10)      6.5 1   Q.3( 10)      6.6 ±   0.4C 10)      6.5  s   Q.4<  9)
  (S/dl)

    ALi        3.8 ±   0.2< 10)      3.7 ±   0.2( 10)      3.8 1   0.2C 105      3.8  ±   0.1(  9)
  Ca/dl)

   GLOB        2.8 ±   0.4( 103      2.8 *   0.2C 103      2.8 t   0.2< 10>      2.7  i   0.3{  9)
  (9/dl)

 ALB/GLOB    1.364 * 0.162C 105    1.314 * 0.126C 10)    1.355 t 0.114( 10)    1.419  * 0.124C  93
  (ratio5

    CHOL      70.0*  13.7(10)     65.3 t  11.0(10)     58.9 ±  14.3(10)    70.9*  13. 4(  9)
  (mg/dl)
* •• Statistically significant difference from control  group
     using ANOVA and Dunnett's T-Test 
-------
                                                                        Study No. 5221.06
                                   TABLE 14 (CONTINUED)
                  SUBCHRONIC TQXJCITY OF ORTHO-CRESOL IN SPRABJE OAWIIY RATS
                               MALE CLINICAL CHEMISTRY VALUES
                                      [Interim Sacrifice]
 Parameter     0 mg/kg/day         50 mg/ks/diy         175 mg/kg/day       600 mg/kg/day
   D  BIL     0.02 i 0.01  (10)     0.02 *  0.01 (10)    0.02 ± 0.01 C10)    0.02 * 0.01  (9)
  (mg/dl)

   T  BIL     0.15 t 0.04  (10)     0.16 1  0.04 (10)    0.14 t 0.05 (103    0.16 ± 0.04  (9)
  (mg/dl)

     CA      12.4 ±  1.4  (10)     12.6 *   1.5 (10)    13.1 i  1.6 (10)    12.4 ±  1.1  (9)
  (mg/dl)

     Na       145 t  5 (10)       145  t  6 (10)        152  ±  14 (10)    146  t  7  (9)
  (Meq/l)

    K        7.9±  1.4(10)      7.7 i   1.7(10)     7.2*  1.5(10)    7.9*  2.2(9)
  (Meq/l)

    CL       101 t    4 (10)      101 ±     5 (10)     102 i   8 (10)    102 t    7  (9)
  (Meq/l)

AU PHOS    141  ±  53 (10)      127  t   81  (10)      152  i  81  (10)      124   t  77 (9)
   C02       26  ±  3 (10)        24  ±   3.4  (10)     25  t  4  (10)       24  i  5 (9)
 (Meq/l)

  CREAT     0.71 ± 0.07 (10)    .  0.74  t  0.09  (10)     0.70 t 0.07  (10)    0.71 i 0.07 (9)
 (mg/dl)

  .PHOS     10. B i  0.6(10)      10.0*   1.1(10)     10.6 t  0.9(10)    10.7*  1.3(9)
 (mg/dl)
    Results presented as  mean t standard deviation  ( N  )
                                                 31

-------
                                                                                     Study No. 5221.06
                                             TABLE 15
                    SUBCHRON1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE  DAULEY RATS
                                  MALE CLrSICAL CHEMISTRY VALUES
                                       [Terminal Sacrifice]
Parameter       0 mg/hg/day          50 mg/kg/day          175  mg/kg/day         600 mg/kg/day

   CLU      236.8 ±  58. 1< 10)    226.2 i  59. 9< 10)     248.3 i 33. 2(  10)    187.5 ±  '43. U 10}
 (mg/dl)

   BUN       14.3 i   2. K 10)     12.fi ±   2.6< 10)      13.8 t  2.0C  10}     14.1 *   2.6C 10)
 Cmg/dl)

  SGPT         80 ±   144( 10)       35 t    2?< 10)        39 i   22(  10)       88 ±   179C 10)
 (lu/l)

  SCOT        130 i   161( 10)       85 t    56< 10)        85 1   24(  10)      137 ±   2Q4< 10)
  T PRO   •    6.7 t   0.7< 10)      6.Z t   1.0C  10)      6,7 *   0.4(  10)      6.3 ±   0.7C 10)
 (i/dl)

   ALS        3.7 t   0.3( 10)      3.3 ±   0.3(  10)      3.7 i   0.2(  10)      3.6 ±   0.3C 10)
  GLQB        3.0 ±   0.4( 10)      2.4 t    0.9C  10)      3.0 t   0.3C 10)      2.7 i   0.5( 10)
 Cg/dl)

ALB/GLOi    1.258 t 0.095< 10)    1.818 t  0,819(  10)*    1.248 J 0.125( 10)    1.351 ± 0.231C 10)
 (ratio)

   CHOL      82.7 ±  24. 1< 10)     70.8 i   17.0(  10)     69.2 ±  12. 3( 10)     83.0 ±  27.3C 1C)
 (mg/dl)
 --  Statistically significant  differtnce  from control group
    using ANOVA and Ounnett's  T-Test  
-------
                                                                                   Study Mo.  5221.06
                                     TABLE 15  (continued)
                  SUBCHRONIC TOXICITY OF  QRTHQ-CRESOl  IN SPRA2UE DAUIEY RATS
                                HALE CLINICAL  CHEMISTRY VALUES
                                     [Terminal  Sacrifice]
  Pen-meter      0 ms/kg/day        50  mg/kg/day        175 mg/kg/diy       600 rng/kg/day

    0 B1L     0.02 i O.OH  10)   •  0.01  i  Q.OU  103*   0.01 ± O.Q1( 10)    O.DE ± 0.01(  10)
   (mg/dl)

    T Bll     0,10 ± O.Q4(  10)     O.Q8  i  Q.03(  10)    0.09 i 0.04( 10)    0.11 i 0.07(  10)
   (mg/dl3

      Ca       12.1  *  1.K  10)     12.6  t  0.9(  10)    12.4 t  1.3< 10)    11.7 i  1.1(  10)
   (mg/dl)

      Na        152  *   7C  10)      151  t    6<  103     153 ±    5( 10)     155 t    7C  93
   (Heq/l)

      K         9.1  t  2.3(103     7.4  i  1.4(10)     8.2*  1.7(10)     7.5 i  1.3(  9)
   (Heq/l)

      Cl        100  i   6(  103      99  t    6(  10)     101 1    4( 10)      99 t    5(  9)
   (Heq/l)

 ALK PHOS      95  t   49(  10)      74  *   33( 10)      78 t   35( 10)      70 t  32(  10)
   Uu/l)

     C02        21 ±    4(  10)      21  *    2( 10)      23 t    3( 10)      22 s    3<  93
   (Heq/l)

   CREAT     0.75 1 0.06(  10)    0.72  t Q,1Q< 10)    0.71 ± 0.08C 10)    0.71  t 0.08(  10)
   (mg/dl)

    PHOS     10.0 t  1.3( 10)     8.2 *  1.1( 10)*   9.9 t 1.9( 10)     9.3 1  1.2C  10)
   (mg/dl)
* •- Statistically significant difference from control  group
     using ANOVA and Dunnett's T-Test CP<=0.05).

     Results presented as mean 1 standard deviation ( N 3
                                            33

-------
                                                                                      Study No.  5221.06
                                             TABLE  16
                     SUBCHRONIC TOXICITY  OF CRTHO-CRESOL  IN SPRACUE OAKLEY RATS
                                  FEMALE  CLINICAL  CHEMISTRY VALUES
                                         [Interim  Sacrifice]
 Parameter       0  mg/kg/day           SO mg/kg/day          175 mg/lcg/day         600 mg/kg/day

    GLU       160.9  t  43. OC 10)    194.2 ±  69. 9< 10)    179.2 ±  41. 3< 10)    215. S *  69. 21   7)
  (mg/dt)

    BUN        14.9  ±   3.0C 10)     16.7 ±   2.3< 10)     16.9 *   4.1( 10)     14.9 ±   2.3C   7)
  (mg/dt)

  SCPT         35  ±     7( 10)       34 *    10( 10)       40 *    11( 10)       46 t    13C   7)
  CIu/l)

  SGOT         74  ±     4( 10)       71 t    14( 10)       81 i    11( 10)       78 ±     9(   7)
  T PSO       6.8 *   0.4C 10)      6.8 ±   0.6( 10)      6.9 ±   0.7C 10)      6.9  t    0.6C  7)
 (g/dl)

   ALB        4.1 t   0.2C 10)      4.1 ±   0.3( 10)      4.1 t   0.3C 10)      4.0  ±    0.7C  7)
 (g/dl)

  GL08        2.7 ±   0.3( 10)      2.7 t   0.4( 10)      2.7 ±   0.4( 10)      2.7  t    0.3C  7)
ALB/GLOB    1.534 ± 0.183( 10)    1.564 ± 0.193< 10)    1.533 t 0.170(  10)     1.499 t Q.264C  7)
 Cratio)

   CHDL      80.3 ±  12.9( 10)     75.5 t  27.f( 10)     81.7 ±  11. 1(  10)     85.9 ±  14. 2C  7)
 (mg/dl)
    Results presented as mean *  standard deviation (  N  )
                                            34

-------
                                                                      Study No. 5221.06
                                    TABLE 16 (continued)
                 SU8CHSOK1C TOXICITY OF ORTHO-CSESOL IN SPRAGUE DAULEY  RATS
                              FEHALE CLINICAL CHEMISTRY VALUES
                                     [Interim Sacrifice]
Parameter      0 mg/kg/day        50 rng/kg/day        175  mg/kg/day       600 mg/kg/day

   D Ell     0.01 t 0.01  (10)    0.02 t 0.02 (10)     0.02  ± 0.02  £10)    0.01 i 0.01 (7)
  (mg/dl)

   T BIL     0.14 * 0.05  (10)    0.15 i 0.04 (10)     0.15  t 0.04  (10)    0.18 * 0.04 (7)
  (mg/dl)

     Ca      14.0 ± 1.1 (10)     12.8 ±  1.7 (10)     13.1  i   1.1  (10)    13.4 ±  1,3 (7)
  (mg/dl)

     Na       147 i 8 (10)        153 ± 14 (10)        156  ± 20  (10)       144 i  3 (7)
  (Heq/l)

     K        8.9 i 2.0 (10)      8.4 t  1.1(10)      8.6  i   1.1(10)     8.5 ±  1.2(7)
  (Heq/l)

     Cl       104 ± 8 (10)        108 t   14 (10)      112  i   19  (10)     101 *    4 (7)
  CKeq/l)

 ALK PHOS      93 t   29  (10)     111 ±   94 (10)      104  *   52  (10)      94 t   32 (7)
  CIu/l)

    C02 -       22 s    3  (10)     23 ±    3 (10)       21 i   4 (10)      20 i.    4 (7)
  (Meq/l)

   CSEAT     0.67 i 0.06  (10)    0.69 * 0.07 (10)     0.72  t 0.09  (10)    0.75 i 0.09 (7)
  (mg/dl)

    PHOS     10.21  0.9(10)     9.64  1.2(10)     10.0  ±   0.8(10)     9.6 ±  0.6(7)
  (ingM)
    Results presented as mean  i standard deviation ( M )
                                            35

-------
                                                                                      Study No. 5221.06
                                             T/.BLE 17
                    SUBCHRON1C TOX1CITY OF CRTHO-CRESOL IH SPRAGUE DAULEY RATS
                                 FiHALi CLINICAL CHEMISTRY VALUES
                                        [Terminal Sacrifice]
Parameter       0 rag/kg/day          50 mg/kg/day          175 mg/kg/day        600 mg/kg/day

   GLU      177.0 t  47. 6C 103    1B5.3 ±  45. 7< 10)    193.5  1  43. 9(  10)     150.1 t  18. 7(  4)
   BUM       14.6 t   1.4C 10)     13.2 *   3.2( 10)     15.7 ±    3.2C  103      16.4 t   2.7C  43
 (mg/dl)

  SGPT         24 *     4( 10)       32 t    17C 10)       40 t     23{  10)       30 ±    11(  4)
 Clu/l)

  SCOT         75 *    15( 10)       86 ±    26( 10)       93 t     40{  10)       83 ±    29C  4)
 CIu/l)

  T PRO       6.7 ±   0.9{ 10)      6.8 t   0,9< 10)      7.4 *    0.7(  10)      6.8 ±   0.7C  4)
 (i/dl)

   ALB        4.2 1   0.4{ 10)      4.4 1   0.3( 10)      4.4 t    0.4(  10)      4.1 ±   0.4C  4)
 
-------
                                                                                  Study Ho. 5221.06
                                   TABLE 17 (continued)
                 SU8CHRONIC TOXICITT OF ORTHO-CRESOL JN SPRAGUE DAWLEY BATS
                             FEMALE CLINICAL CHEMISTRY VALUES
                                   [Terminal Sacrifice]
 Parameter       0 mg/kg/day        50 mg/kg/day        175 mg/kg/day       600  mg/kg/day

   0  B1L      0.01 ± O.OK 10}    0.01 t O.OK 10}    0.02 ± 0.01C 10}     0.01 ± O.OH  4)
  (mg/dl)

   T  BIL      0.09 t 0.04( 10}    0.09 t O.Q3£ 10)    0.09 i 0.06< 10}     0.09 i 0.04C  4}
  (mg/dl)

     CA       13.0 ±  1.0( 10}    13.2 i  0.9C 10}    13.2 t  1.5( 10)     12.4 i 1.2(  4)
  
-------
                                                                                  Study Ho, 5221.06
                                          TABLE  18
                 SUBCHROM1C TOXICITY OF ORTHO-CRESOL  IN SPRAGUf DAWLEY RATS
                  RELATIVE  HALE  ORGAN WEIGHT DATA «  Terminal Body Weight)
                                    [Terminal Sacrifice]
Organ
HEA8T
LIVES
SPLEEN
KIDNEY-LFT
KIDNEY-RT
TESTIS-LFT
TESTIS-RT
ADRENALS
BRAIN •
THr./PARA.
0 mg/kg/day
0.318 t
3.337 ±
0.142 *
0.365 ±
0.370 *
0.312 ±
0.317 *
0.010 i
0.40S *
0.006 ±
0.02K
Q.246C
o.om
0.036C
0.034C
Q.Q39C
0.029C
0.002(
0.027C
0.002C
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
50
0.332
3.450
0.150
0.386
0.395
0,318
0.325
0,011
0.423
0.006
mg/kg/day
± 0.09U
1 0.911s;
4 0.042C
* 0.11K
± 0.118C
* 0.120C
i 0.123C
* 0.004C
* 0.09BC
± 0.003(
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
175 rag/kg/day
0.315
3.315
0.133
0.384
0.382
0.319
0.319
0.010
0.404
0.006
t 0.027C
i 0.271C
± 0.014{
± 0.038C
1 0.037C
i 0.032C
± 0.032C
I 0.002C
i 0.037(
± O.OOK
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
600 mg/kg/day
0.324 t Q
3.524 i 0
0.139 i 0
.019( 12)
.318( 12)
.012( 12)
0.423 ± 0,037< 12)
0.429 t 0
0.340 * 0
0.337 i 0
0.011 s 0
0.432 t 0
0.006 t 0
.039C 12)
.033C 12)
.035C 12)
.001 ( 12)
.031 ( 12)
.001 ( 12)
Results presented as mean i standard deviation ( N )
                                        38

-------
                                                                                Study  No. 5221.06
                                              TASLi 19
                     SUBCHSONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE  DAWLEY  RATS
                     RELATIVE FEMALE ORGAN WEIGHT DATA C% Terminal Body Weight}
                                        CTerminal Sacrifice]
Organ
HEART
LIVER
SPLEEN
KIDNEY-LFT
KIDKEY-RT
OVARY -LFT
OVARY -ST
ADRENALS
BRAIN
THY.
0 mg,
0.354 *
3.205 1
0.191 ±
0.384 t
0.396 *
0.016 *
0.016 i
0.024 t
0.762 S
0.009 ±
^kg/day 50 mg/kg/day ,
0.038<
0.240(
0.017<
0.045<
0.053<
0.006(
0.005<
Q.004C
Q.042C
0.003C
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
0.367
3.148
0.178
0.382
0.394
0.014
0.015
0.022
0.673
0.008
* Q.04SC
i 0.199C
i 0.019C
± Q.030C
± 0.037C
t 0,005(
* 0.004<
± 0.005(
± 0.10U
t 0.002C
20)
20)
20)
20)
20)
19)
18)
20)
19)*
20)
175 mg/lcg/day
0.357 t
3.218 i
0.194 ±
0.390 t
0.413 t
0.016 ±
0.017 t
0.023 *
0.720 t
0.009 i
Q.Q37C
0.255C
0.024C
0.049C
0.068C
0.005C
0.004C
0.005C
0.132C
0.003(
203
203
203
205
20)
20)
20)
20)
19)
20)
600 mg/kg/day
0.359 ± 0
3.319 t 0
0.204 i 0
0.388 i 0
0.400 t 0
0.019 t 0
0.014 t 0
0.027 t 0
0.800 t 0
0.011 t 0
.037( 4)
.177C 4)
.038C 4)
.023( 4)
.016C 4)
.C05C 4)
.005C 4)
.002( 4)
-034C 4)
,002( 4)
* •• Statistically significant  difference from control group
     using ANOVA and Dunnett's  T-Test (P<=0.05).

     Results presented as mean  t standard deviation { N  )
                                                  39

-------
                                                                                      Study Ho. 5221,06
                                             TABLE 20
                    SUSCHROMIC TOXICITY OF ORTHO-CRESOL IK SPRAGUf OAULEY RATS
                                    HALE ORGAN WEIGHT DATA (g)
                                       {Terminal Sacrifice]
Organ
HEART
LIVER
SPLEEH
KIDHEY-LFT
JCIDNEY- RT
TEST1S-LFT
1EST1S-RT
ADRENALS
BRAIN
THY. /PARA.
0 ing/kg/day
1.677 i
17.609 t
0. 747 i
1.924 *
1.951 i
1.642 ±
1.669 *
0.053 i
2.132 t
0.030 t
0.15U
1.848<
0.104<
0.219(
0.23K
0.196<
0.1 2B(
0.011(
0.095C
0.010C
20)
20)
20)
20)
HO)
203
20)
20)
20)
20)
50 mg/kg/day
1.694 *
17.713 *
0.768 i
1.967 i
2.010 i
1.610 i
1.649 ±
0.054 t
2.159 t
0.030 ±
0.174<
2.679C
0.118C
0.228<
0.249<
0.34H
0.337C
0.009(
0,089(
0.009C
20)
20)
205
20)
20)
203
20)
20)
20)
20)
175 mg/kg/day
1.716 t
18.096 ±
0.755 ±
2.094 ±
2.085 t
1.730 t
1.729 *
0.054 t
2.189 t
0.031 t
0.17U
2.195C
0.093C
0.265C
0.256{
0.117C
0.109C
0.009(
0.08K
0.006C
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
600 mg/kg/day
1.595 ±
17.351 i
0.683 t
2.080 t
2.107 t
1.663 t
1.652 t
0.052 1
2.112 ±
0.031 ±
0.170C 12)
2.494C 12)
0.072( 12)
0.277C 12)
O.Z74< 12)
0.164( 12)
0.1 72< 12)
0.006( 12)
0.073< 12)
0.007C 12)
Results presented as mean ± standard deviation <  N
                                          40

-------
                                                                                    Study No.  5221.06
                                                TABLE 21
                       SU8CHROMIC TOXICITY OF ORTHO-CRESQL IN SPRAGUE DAULET RATS
                                      FEHALE ORGAN WEIGHT CATA (g)
                                           [Terminal Sacrifice]
Organ
HEART
LIVER
SPLEEN
KIDNEY-LFT
KIDNEY-RT
OVARY -LFT
OVARY -RT
ADRENALS
BRAIN
THT./PARA.
0 mg/kg/day
0.917 t
8.295 i
0.492 ±
0.991 ±
1.023 t
0.042 *
0.042 i
0.062 t
1.968 ±
0.025 *
C.112<
0.770(
0.04Q<
0.122C
0.139C
0.018C
0.015C
0.010C
0.033C
Q.Q07C
205
20)
20)
205
20}
205
20}
20)
205
20}
50 mg/kg/day
1.039 ±
8.923 t
0.505 t
1.084 t
1.118 ±
0.041 ±
0.042 t
0.062 t
1.913 ±
0.023 t
0.145<
1.027C
0.070(
0.133<
0.149(
0.013t
0.01U
0.01U
0.285(
0.006<
205*
205
205
205
205
195
18)
205
195
205
175 mg/kg/day
0.952 t
8.603 *
0.517 t
1.037 ±
1.100 ±
0.043 ±
0.044 1
0.060 t
1,899 ±
0.025 ±
Q.12QC
1.113C
0.066(
0.1 28<
0.197C
0.012(
0.011C
0.011C
0.2S3C
0.006{
205
20)
205
205
205
205
205
20)
19)
20)
600 mg/kg/day
' 0.873 *
8.067 *
0.497 ±
0.944 ±
0.971 ±
0,046 i
0,033 ±
0.066 t
1.941 ±
0.026 ±
0.124C 45
0.734C 4)
0.104( 4}
0.090C 4)
O.OSZ( 45
O.OHC 45
0.012C 45
0.005C 45
0.01'C 45
0.006( 4)
* •• Statistically significant difference from control  group
     ysing ANOVA and Dunnett's T-Test (P<=0.055.

     Results presented as mean i standard deviation <  M 5
                                                 41

-------
                        'Table 22
 Subchronic Toxicity of Ortho-Cresol  in Sprague Dawley Rats
                  Clinical  Chemistry  Values
                        [Baseline!

                  Hales             Females

   T  PBO     5.5 + 0.4  (10)      5.6 + 0.3 (10)
  (g/dl)

   ALB       3.5 + 0.2(103      3.7+0.4(10)
  (g/dl)

   GLOB       2.0+0.3(10)      1.9+0.5(10)
  (g/dl)

 ALB/GL08     1.8 + 0.3  (10)      2.2 + 1.1 (10)
 (ratio)

   BUM      10.7+1.8(10)     13.7+2.1(10)
  (mg/dl)

   T  BIL    0.31 + 0.05  (10)    0.23 + 0.05 (10)
  (mg/dl)

   D  BIL    0.08 + 0.06  (10)    0.05 + 0.04 (10)
  (mg/dl)

   GLU      66.0+9.3(10)     71.3+11,7(10)
  (mg/dl)

   CREAT    0.61 + 0.06  (10)    0.64 + 0.03 (10)
  {mg/dl )

   SGPT       41 + 8 (10)         40 + 7 (10)
  (lu/D

   SCOT       82+8 (10)         83+9 <10)
  CHOL     68.0 + 13.5 (10)    75.4 + 10.0 (10)
 (mg/dl)

ALK PKOS    226 + 49 (10)       186 + 38 (10)
 CIu/l)
Results presented as mean + standard deviation (
                            42

-------
                            Table 23
    Subchronie  Toxfcity of Ortho-Cresol in Sprague Oawley Rats
                        Hematology Values
                            [Baseline]

                     Hales              Females

      SBC       7.04 + 0.65 (10>    6,84 + 0,38 <10>
 (x  1(

       HGS       14. S + 1.1 (10)     14.5 + 0.5 (10)
      HCT       43.6+3.2(10)     42.0+1.6(10)
      «)

      me       15.5 + 3.0(10)     11.6 + 3.0(10}
 (x
     SECS        1.7+0.9(10)      0.9+0.5(10}
(x 10A3/imr3>

    BANDS        0.0 + 0.0 (10)      0.0 + 0.1  (10)
(x 1
   LYMPHS       13.4 + 2.8 (10)     10.3 + 2.5  (10)
(X 1
    MONO         0.3 + 0.2 (10)      0.3 + 0.2  (10)
(x 1
     EOS         0.1*0.2(10)      0.0 +  0.1(10)
(x 1
    RETIC        1.1+0.5(10)       1.5+0.7(10)
   <% R8C)
Results presented as mean + standard deviation ( N
                            43

-------
                  QUALITY ASSURANCE STATEMENT
Study Title:  Subchronic Toxicity of Ortho-Cresol in
              Sprague Dawley Rats
Study Number: 5221.06

Study Director:  L.  Thomas Mulligan,  Ph.D.

Initiation Date:  September 16,  1985

Review Completed Date:   January  9,  1987
     This study has been divided into a series of phases.  Using a
     random sampling approach,  Quality Assurance monitors  each  of
     these phases over a series of studies.  Procedures,  documenta-
     tion, equipment,  etc.,  are examined in  order to assure that the
     study is performed in accordance with the U.S.  FDA  Good
     Laboratory Practice regulations {21CFR58),  the  U.S. EPA GLPs
     (40CFR792 and 40CFR160),  and  the OECD guidelines and  to assure
     that the study is conducted according to  the protocol.

     The  following are the inspection dates, phases  inspected,  and
     report dates of QA inspections of this  study.
                                     Microbiological  Associates,  Inc,

-------
                          DATES/PHASES


INSPECT OH 85/09/27 - 85/09/27,TO STUDY DIE 85/09/27,TO MCMT 85/09/27

PHASES: PROTOCOL REVIEW


INSPECT ON 85/11/12 - 85/ll/12,TO STUDY DIE 85/11/12,TO MGMT 86/01/03

PHASES: BODY WEIGHTS
        ANIMAL OBSERVATIONS

INSPECT ON 86/04/07 - 86/04/10,TO STUDY DIR 86/04/10,TO MGMT 86/08/15

PHASES: DATA REVIEW


INSPECT ON 86/08/04 - 86/08/07,TO STUDY DIR 86/08/07/TO MGMT 86/08/15

PHASES; DRAFT REPORT


INSPECT ON 87/01/07 - 87/01/07,TO STUDY DIR 87-/01/07,TO MGMT 87/01/09

PHASES': DRAFT TO FINAL REPORT
                                    -Microbiological Associates, Inc.

-------
This report describes the methods and procedures used in the
study and the reported results accurately reflect the raw data
of the study.
        Quality Assurance                 Date
        RA/QA Department
                                -Microbiological  Associates,  Inc,

-------
                                                Study No.  5221.06
                       APPENDIX A

TWO-WEEK RANGE-FINDING/EXPICiRATORY STUDY OF ORffiO-CRESOL
                 IN SPRAGUE BAWLEY RATS

-------

-------
                                                                                                                   Study No. 5221.06
                             TWO WEEK  RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL  IN SPRAGUE DAWLEY RATS
                                                      MALE BODY WEIGHT DATA   (g)
TEST
DAY
DAY 1
DAY 8
DAY 14
0 mg/kg/day
160.2 i 5.1(
219.1 t 6.0C
271.6 t 10. 9(
10)
105
10)
5 ng/kg/day
153.8 t 7.4{
Z13.4 * 11. 7(
265.0 ± 19. 7(
10)
10)
10)
10 mg/kg/day
154.4 * 5.6{
214.9 ± 14. 5<
267.0 t 21 .3(
10)
10)
10)
25 mg/kg/day
154.4 t 7.7{
218.0 t 19. 4{
275.7 ± 30. B(
10)
10)
10)
50 mg/kg/day
158.4 t 7.5{ 10)
221.5 t 10. 2{ 10)
278.5 ± 20.3C 10)
100 mg/kg/day
156.4 * 4.5(
214. 9 * 12. 7{
262.5 t 21 .9(
10)
9>
9)
Results presented as mean * standard deviation ( N )

-------

-------
                                                                                                                                   Study No. 5221.06
l
U!
                                             TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL  IN  SPRAGUE DAWLEY RATS
                                                                      FEMALE BODY WEIGHT DATA  (g>

                 TEST
                 DAT           0 mg/kg/day           5 mg/kg/day          10 mg/kg/day          25 mg/kg/day          50 mg/kg/day          100 mg/fcg/day

                DAT  1       116.2  ±    B.1<  10)    117.6 t   5.4( 10)    118.5 i  10.2( 10)    118.1  ±  10.5( 10)     119.4  ±    5.B(  10)    117.2 i   7.0( 10)

                DAY  8       164.1  i    9.8(  10)    163.9 ±   9.01 10)    159.8 ±  10.2( 10)    162.2  t  13.6( 10)     165.2  t   10.5(  10)    162.1 ±  12.U 10)

               DAY  14       191.6  ±   10.3(10)    192.0*  11.8(10)    190.2*  13.5(10)    191.5  t  16.0(10)     192.7  t   11.9(10)    191.2*  15.7(10)
                 Results presented as mean 1  standard deviation ( N )

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                                                                                                                Study No. 5221.06
                         TWO WEEK RANGE-FIND ING/EXPLORATORY  STUDlf OF  ORTHO-CRESQL  IN  SPRAGUE DAWLEV RATS
                                               MALE  FOOD  CONSUMPTION  DATA (g/day)

 TEST
 WEEK          0 ing/kg/day         5 mg/kg/day        10  mg/kg/day         25  mg/kg/day        50 mg/kg/day         100 mg/kg/day

yEEK  1      21.9 t  1.9{ 10)    23.1 *   4.5(  10)     22.6 t   3.2( 10)    22.1 t  3.2< 10)    23.5  t   2.4( 10)     20.8 t  4.9(  10)


WEEK  2      25.5 t  2.4( 10)    25.6 l   2.8(  10)     25.5 t   3.3{ 10)    27.3 *  4.9C 10)    26.4  t   3.9( 10)     25.7 l  2.3(  9)
  Resutts presented as mean t standard deviation (  N )

-------
                                                                                                               Study No. 5221.06
                         TWO WEEK RANGE-FIHOI NO/EXPLORATORY  STUDY OF ORTHO-CRESOL  IN SPRAGUE OAWLEY RATS
                                              FEMALE FOOD CONSUMPTION DATA  (g/day)

 TEST
 UEEK          0 mg/kg/day         5 mg/kg/day        10 mg/kg/day        25 mg/kg/day        50 mg/kg/day        100 mg/kg/day
WEEK  1      19.8 t  4.4( 10)    17.8 t  1.6( 10)    18.3 t  1.9(  10)     20.0  ±  4.5<  10}    19.6 *  3.3( 10)    18.4 *  2.9( 10}


WEEK  2      25.0 ±  9.6( 10)    19.7 t  1.9( 10)    23.S t  9.2{  10)     22.0  ±  4.9(  10)    24.6 ±  8.2( 10)    22.8 t  6.1C 10)
  Results presented es mean t standard deviation ( N )

-------
TWO WEEK RANGE-HNDING/EXPLQRATQRY STUDY OF  ORTHO-CRiSOL  IN  SPRACUE  DAWLEY SATS
               KALI SOOY WEIGHT DATA  (g)
                  ANIMAL NUMBER  DAY  1   DAY  8  DAY  14
   DOSE LEVEL
   0 mg/kg/day
   5 rng/kg/day
  10 mg/kg/day
  25 mg/kg/day
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
2177
2178
2179
2180
2181
2182
2183
2184
2185
21 66
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
161.9
164.2
160.8
154.5
166.8
158.2
152.7
160.3
155.1
167.5
163.7
153.1
143.1
142.7
148.9
152.8
156.2
157.1
155.8
164.2
161.1
154.9
150.9
165.1
154.1
145.9
157.7
149.8
151.7
152.6
156.4
150.6
159.4
141.5
144.2
162.9
150.6
165.0
158.6
154.9
227.1
211.3
216.6
213.8
220.2
225.1
210.4
221.7
219.4
225.6
223.5
222.8
208.2
192.1
207.6
210.6
222.7
208.7
205.7
232.1
220.3
222.7
224.1
235.7
220.0
198.6
215.4
217.2
183.9
211.1
213.6
199.8
245.3
194.7
202.4
245.3
234.0
199.1
229.5
216.4
2S6.8
257.1
255.5
265.5
274.7
280.6
261.6
281.5
277.3
275.6
288.1
275.0
263.1
229.8
250.7
270.9
276.5
254.0
248.1
294.1
271.3
273.9
277.7
301.3
279.1
250.1
260.7
276. D
220.8
259.6
242.5
267.6
325.6
244.3
254.9
312.9
299.4
243.6
296.4
269.6
                                   A-6

-------
 MEEK RANGE-FINDING/EXPLORATORY  STUDY Of QRTHQ-CRESOL IH  SPRAGUE DAMLEY RATS
           MALE BODY yglGHT DATA  
-------
TWO WEEK RANGE-FINDING/EXPLORATORY  STUDY  OF  ORTHO-CiESOL  IN SPRAGUE DAULEY RATS
              FEMALE'BODY WEIGHT  DATA   (g)
                  ANIMAL NUMBER  DAY   1   DAY   8   DAY   14
   DOSE LEVEL
   0 mg/kg/day
   5 mg/kg/day
  10 mg/kg/day
  25 mg/kg/day
2221
2222
2223
2224
2225
2226
2227
2223
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
103.5
113.9
107.9
116.1
116.3
117.8
121.5
109.6
130.2
125.5
118.9
107.9
111.2
123.6
114.0
119.9
116.3
117.0
123.6
123.6
112.6
110.4
135.4
126.8
132.5
114.9
110.9
122.0
104.9
114.4
110.2
127.1
113.9
128.6
109.8
110.2
124.9
109.5
137.7
109.1
152.6
152.2
157.1
168.7
169.4
167.3
170.9
152.1
179.5
170.9
170.2
145.3
155.5
165.9
165.5
161.1
161.9
163.8
171.8
177.6
161.0
152.7
148.5
172.6
180.2
147.4
159.2
160.1
155.0
161. S
147.8
161.1
165.5
174.3
150.8
152.1
171.6
191.0
153.5
154.0
175.0
178.6
191.4
195.0
199.3
196.1
200.5
179.1
204.7
196,0
205.2
170.4
182.9
1S6.7
197.5
188.7
192.8
184.1
208.1
203.4
189.3
182.2
190.9
205.6
215.8
165.0
189.8
189.4
183.7
190.4
179.1
192.5
192.2
208.8
181.2
174.0
198.7
224.3
174.3
190.0
                                      A-8

-------
TWO WEEK RANGE-FIND I KG/EXPLORATORY  STUDY OF QRTHQ-CRESOl IN SPRAGUE DAyiEY  RATS
              FEMALE'BODY WEIGHT  DATA   Cg)
                  ANIHAL NUMBER   DAY   1  DAY  8  DAY  14
   DOSE LEVEL
  50 mg/kg/day
  100 mg/ks/day
2261
2262
2263
2264
2265
2266
2267
2268
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
22BO
121.5
111.4
112.5
127.6
122.4
122.5
122.1
117.8
111.5
124.4
109.0
111.9
126.3
121.7
121.9
125.7
116.0
106.0
120.2
113.2
162.3
147.8
165.2
173.4
172.8
172.4
169.4
161.7
H8.2
178.9
149.2
160.6
1B0.6
178.0
159.1
175.2
160.6
144.8
155.4
158.0
196.8
172.0
198.4
201.8
201.5
202.7
192.3
186.9
172.4
201.8
177.7
190.6
210. 7
205.7
192.6
212.4
189.1
161.2
182. 6
189.5
                                    A-9

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TWO MEEK RANGE-FINDING/EXPLORATORY STUDY OF  ORTHQ-CRESQL  IN  SPRAGUE DAWLEY RATS
       HALE FOOD CONSUHPT10N DATA (g/dayj
                  ANIMAL NUMBER  UEEK  1   WEEK   2
   DOSE LEVEL
   0 mg/kg/day
   5 nig/kg/day
  10 mg/kg/day
  25 mg/kg/day
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
21 77
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
24.2
18,5
19,4
21.6
22.1
'21.5
21.9
21.5
24.9
23.1
22.9
23.9
20.7
18.0
22.6
34.8
20.7
21.4
22.4
23.7
22.6
21.2
22.5
22.9
24.9
17.5
28.7
22.9
18.1
24.5
20.6
17.4
28.1
19.1
22.2
25.8
21.0
20.1
24.2
22.9
27^0
20.8
22.4
26.4
26.7
24.2
25.2
26.7
28.2
27.5
27.6
27.5
24.1
20.2
26.9
27.1
26.4
26.1
21.6
28.7
27.2
25.3
25.8
30.4
27.6
21.9
23.4
25. S
19.1
28.6
24.3
22.5
34.6
23.7
28.0
35.8
29.3
21.3
28.3
25.5
                                A-10

-------
TWO WEEK RANCE-F1NDINC/EXPLORATORY STUDY OF ORTKQ-CRESOl  IN SPRAGUE 0AWLEY RATS
      MALE FOOD  CONSUMPTION DATA (g/day)
                ANIMAL NUMBER  WEEK  1   MEEK  2
   DOSE LEVEL
50 mg/kg/day 2201
2202
2203
2204
.2205
2206
2207
2208
2209
2210
100 mg/kg/day 2211
2212
2213
2214
2215
2216
2217
2218
2219
2220
21,5
22.2
24.4
28.1
25.7
20.6
26.3
22.7
21. §
22.2
27.7
19.6
21.2
22.8
21.4
22.9
24.5
17.8
21.0
9.1
22.5
25.4
23.3
35.4
26.6
24.5
30.4
26.4
23.9
25.3
25.4
24.5
25.4
23.0
25.1
27.7
28.8
22.5
28. 9
na
   na  =  no  data  available.
                             A-ll

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  TWO WEEK RANGE-FINDING/EXPLORATORY STUDY  OF  ORTHO-CRESQL  IN SPRAGUE DAULEY RATS
                          MALE FOOD CONSUMPTION  DATA  (g)
                                 CFeeder Ueightsl
                ANIMAL NUMBER  new feeder 1   old feeder  1  new  feeder 2  old feeder 2
 DOSE LEVEL
 0 mg/kg/day
 5 mg/kg/day
10 mg/kg/day
25 mg/kg/day
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
Z176
2177
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
219S
2199
2200
490.3
518.9
512.7
483.7
504.0
447.1
498.7
403.5
475.3
506.9
507.7
508.4
539.7
468.1
469.7
451.0
499.5
465.6
495.6
475.9
490.8
513.7
512.2
521.4
507.3
460.4
575.7
461.1
475.4
485.0
495.2
509.2
457.3
520.4
519.8
506.6
495.6
505.6
499.7
531.4
320.6
389.2
376.9
332.5
349.4
296.5
345.1
252.7
301.3
345.3
347.3
340.8
395.1
341.8
311.6
207.3
354.3
315.8
339.0
310.2
332.4
365.3
354.6
361.0
333.2
338. 2
374.5
300.7
348.6
313.6
351.3
387.1
260.6
386.6
364.3
325.9
348.9
364.6
330.2
371.4
457.6
551.4
564.1
530.4
519.2
478.6
497.4
449.2
509.6
498.1
539.2
520.6
598.5
481.7
491.1
471.4
553.8
537.9
525.4
481.4
510.3
524.9
510.0
521.4
505.8
537.5
530.0
493.4
510.0
514.7
545.8
560.4
450.6
526.9
532.6
495.0
496.7
499.1
510.8
500.1
295.7
426.7
429.7
372.0
359.0
333.6
346.2
289.0
340.7
333.4
373.8
355.7
454.1
360.5
329.9
308.9
395.2
381.3
395.5
309.4
347.3
373.2
355.2
338.9
340.0
405.9
389.7
338.6
395.2
343.2
400.0
425.2
242.9
384.5
364.6
280.2
321.2
371.2
340.8
347.2
                                       A-12

-------
 TWO WEEK SANGE-FINDING/EXPLORATORT STUDY OF ORTHQ-CRESQL IN SPRAEUE DAULEY RATS
                       MALE FOOD CONSUMPTION DATA £g)
                              [Feeder Weights]
              ANIMAL NUH8E8  new feeder 1  old feeder 1  new feeder 2  old feeder 2
DOSE LEVEL
50 nig/ kg/day 2201
2202
2203
2204
2205
2206
2207
2208
2209
2210
100 mg/fcg/day 2211
2212
2213
2214
2215
2216
2217
2218 "
2219
2220
504.7
500.3
516.7
448.5
499.6
532.6
526.0
485.9
504.9
521.5
519.6
522.9
510.5
513.0
543.7
501.8
537.8
543.9
496.7
484.5
354.4
344.7
345.9
251.5
319.9
388.6
341.6
327.0
352.2
366.1
325.7
386.0
362.3
353.6
394.1
341.3
366.4
419.1
349.8
420.9
508.5
493.6
513.9
443.6
501.0
543.8
500.1
455.6
499.6
507.4
509.3
532.7
480.3
522,1
540.8
478.6
510.4
539.3
487.4
na
373.6
341.3
374.3
231.0
341.7
396.5
317.6
297.0
356.0
355.5
356.7
385.6
327.9
384.0
390.4
312.6
337.6
404.3
313.9
na
   na  =  no  data  available.
                                 A-13

-------
TWO UEEK RANGE-FINDING/EXPLORATORY STUDY  OF  ORTHO-CRESOL  IN  SPRAGU6 OAWIEY RATS
      FEMALE FOOD CONSUMPTION DATA (g/day)
                  ANIMAL NUMBER  UEEK  1   WEEK   2
   DOSE LEVEL
   0 ing/kg/day
   5 mg/kg/day
  10 mg/kg/day
  25 mg/kg/day
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249-
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
17.6
31.8
17.1
19.2
19.2
18.6
20.1
16.2
19.3
19,2
18.8
17.3
16.5
16.5
19.2
15.5
17.5
18.1
17.9
20.9
21.4
17.9
16.1
17.9
19.5
15.6
17.1
20.8
18.0
18.4
1B.7
16.5
16.8
18. 8
17.8
16.3
24.2
31.0
20.0
19.5
17.1
19.4
20.6
19.3
37.1
30.8
21.3
45.6
19.2
19.4
20.8
18.3
17.9
17.9
22.0
18.6
20.2
17.4
21.3
22.7
32.1
23.7
46.9
19.5
21.6
15.4
19.9
18.7
21.3
19.4
20.9
20.7
19.2
20.4
19.4
17.6
34.2
26.0
18.4
23.2
                                A-14

-------
TWO WEEK RANGE-FINDING/EXPLORATORY  STUDY  Of ORTHO-CSESOL  IH .SPRAGUE 0AULEY RATS
      FEMALE FOOD CONSUMPTION  DATA  (9/day)
                  ANIMAL NUMBER   WEEK   1  WEEK  2
   DOSE LEVEL
  50 mg/kg/day
  100  mg/kg/day
2261
2262
2263
2264
2265
2266
2267
2266
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
22.3
16.5
17.9
IB. 7
20.0
28.0
18.5
17.9
17.5
18.9
16.7
17.5
24.5
21.6
16.0
18.9
19.7
15.3
15.3
18.4
23.4
18.7
23.5
ZQ.5
22.9
35.7
20.2
43.0
17.8
20.3
21.0
18.2
25.7
35.7
19.7
20.7
29.7
15.4
18.8
23.5
                                A-15

-------
   TWO WEEK RANGE-FlNDtNG/EXPlORATQRY  STUDY OF CRTHO-CSiSQL IN SPRAGUE DAWLEY RATS
                          FEMALE  FOOD  CONSUMPTION DATA  (g>
                                  [Feeder Weights]
                 ANIHAI NUMBER   ne«  feeder 1  old feeder 1  new feeder 2  old feeder 2
  DOSE  LEVEL
  0  mg/kg/day
 5 mg/kg/day
10 aig/ kg/day
25 mg/kg/day
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
513.2
516.9
547.5
516.8
513.3
529.8
517.7
529.4
524.7
498.4
501.6
516.9
538.3
521.8
547.4
510.6
506.6
572.2
536.3
512.6
491.9
438.4
513.4
532.5
551.8
545.7
520.4
562.2
497.9
544.9
508.1
524.6
532.0
506.9
534.8
530.5
463.6
516.9
560.9
535.9
390.1
294.1
427.6
382.2
378.8
399.8
376.7
415.9
389.6
364.2
370.1
395.9
422.9
406.1
413.3
401.9
384.3
445.5
410.8
366.3
342.1
362.8
400.7
407.3
415.4
436.8
400.4
416.5
372.1
416.0
376.9
409.1
414.3
375.3
410.2
416.5
294.5
300.1
421.2
399.4
529.1
457.0
561.1
515.7
535.6
541.2
503.2
538.1
511.8
474.5
483.0
533.5
519.9
491.7
508.4
516.3
527.3
549.2
558.4
488.4
422.7
467.3
518.5
510.4
498.4
516.9
494.4
524.8
483.4
524.1
484.1
509.0
546,2
492.3
502.2
563.3
423.9
414.3
545.6
529.5
426.5
340.4
437.4
400.1
313.0
356.7
375.7
264.5
396.7
358.1
358.2
423.7
412.6
384.2
376.1
404.5
406.2
445.0
430.5
352.0
230.4
324.9
236.9
393.5
368.7
424.7
374.8
412.4
355.4
407.7
358.8
384.7
431.0
370.0
385.8
457.8
218.6
259.1
435.3
390.2
                                      A-16

-------
  TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL  IN  SPRACUE DAUIEY RATS
                         FEMALE FOOD CONSUMPTION DATA (g)
                                 [Feeder Weights]
                ANIMAL NUMBER  new feeder 1  old feeder 1   new feeder 2  old feeder 2
 DOSE LEVEL
50 mg/kg/day
100 mg/kg/day
2261
2262
2263
2264
2265
2266
2267
2263
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
425.1
426.4
538.8
525.2
471.5
503.8
516.1
523.4
442.3
563.7
510.6
433.1
558.0
521.4
485.4
510.9
544.3
468.3
501.9
538.2
268.9
310.6
413.4
394.3
331.7
307.6
386.7
398.4
320.0
431.4
393.5
360.6
386.6
370.5
373.5
378.8
406.4
361.4
395.1
409.2
387.0
411.8
520.7
498.3
459.7
417.8
465.2
495.8
427.7
537.5
485.1
474.5
487.2
469.5
487.6
473.5
493.7
445.6
473.5
490.0
246.9
299.7
379.8
' 375.3
322.4
203.4
344.2
237.6
320.9
415.6
359.2
365.3
333.3
255.6
369.2
349.5
315.7
353.1
361.0
349.1
                                      A-17

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-------
                                    Study No.  5221.06
           APPENDIX B




ANALYTICAL CHEMISTRY 14ETHODOLOCT
           B  - 1

-------

-------
AMERICAN BIOGENIC5 CORPORATION
 ANALYTICAL REPORT

 PROJECT NO.8


 SUBJECT:  	
                       //-fit d
                 ». tr   *

                  ^U/
                   *
                                            PAGE

                                            DATE
Z6IOOOG

OF    J
                                                      3
                                           DEPARTMENT NO.  440

                                       TEST ARTICLE NO. :      ~"
                                 99?*
                                     *
TECHNICIAN
REVIEWED  BY
               ff
                                     Reproduced Irom
                                     best available copy.
                                                            DATE
                                B-2

-------

-------
     American Biogenics
         Corporation
                                March 26, 1986
Dennis D. Dietz, Ph.D.
Technical Program Monitor
Research Triangle Institute
P.O. Box 12194
Research Triangle Park,  NC  27709
Dear Dennis:

     Results
below:


SAMPLE ID
for the  o-cresol confirmatory analyses  are

                          (units mg/ml)
 DILN FACTOR
DILUTION 1
DILUTION 2
                          tabulated
MEAN
C0161A85
C0164A85
C0185A85
C0186A85
C0256A85
C0257A85
C0502A85
C0505A85
C0587A85
C0617A85
C0627A85
C0658A85
C0744A85
C0834A85
C0957A85
C0974A85
100
10,000
2,500
10,000
2,500
10,000
100
10,000
100
100
10,000
10,000
10,000
5,000
10,000
2,500
0
124.7
37.89
130.6
37.89
129.6
0
127.3
0
0
129.9
134.6
127.1
38.8
127.7
36.7, 37.6
0
129.9
38.12
130.6
37.65
133,5
0
125.8, 126.8
0
0
130.8
135.5
125.2
39.0
130.6
36.2
0
127.3
38.0
130.6
37.8
- 131.6
0
126.6
0
0
130.4
135.1
126.2
38.9
129.2
36.9
     The analysis  was  done on a Perkin Elmer 400 HPLC equipped with
a Model 95 UV-VIS  spectrometer set at 221 run.  The separation was
effected on an IBM 250mm  slica column {S/N 2002037)  at a  flow rate
of 2.0 ml/nun of 1% isopropanol/99% hexane.   A 10 uL injection loop
was used for injection.
                              B - 3
                (2171875-3930 « Telex: 250139 « 1BQOE. Pershing Rd •DscaJyr, IL 62526

-------
                                 -2-
     Enclosed  for your information  is  a  sample  of  the  analysis
tracing.

                                  Sincerely  yours,
                                 Edwin A. Wool son,  Ph.D.
                                 Manager, Analytical Chemistry
EAWinssd

Enclosure
                              B - 4

-------
                                                        \\v
               ..__j_
r-
                 -o
                   F
                                                       . , ^.  ,.,^... ....^... -___!£'—-;--

                                                               Reproduced from

                                                               best available copy.

-------
   RCO
L. I
                                                  ENSECO
                                June 2, 1986
Dr. Dennis D, Diets
Research Triangle Institute
? .0. Sox 12194
Research Triangle Park,  NC   277Q9

Dear Dennis ;

     Enclosed please  find a  description of the method we use  for
analysis of compounds by direct  aqueous injection as it pertains
to work perforaed under  SPA  WA-35.

     As you can see,  the analysis procedure is generally the
same for all  compounds differing only in the case of the cresols
which use an  alternate column and temperature program,

     If you have any  questions regarding the method or other
specifics, please do  not hesitate to contact me.
                               Sincerely,
                               W . Henry Camp
                               Analytical Chemist
                               VOA Laboratory
WHC:mk
Encl.
cc:  Dr. Barry Levins  (Microbiological Associates)
     Dr. Dale  Mayhew  (American 3iogenics Corp.!
     Dr. Crosby Thompkins  (Toxieity Research Laboratories
                            B-6

-------
     This method covers  the  determination  of  compounds  by  direct
aqueous  injection.    The  following  co-impounds  can  be   detected
using  column  A, and  temperature  program  A:    acetone,  methyl
isobutyl ketone  (MI3K),  isobutyl alcohol,  methyl alcohol,  ethyl
acetate,  n-butyl  alcohol  and   crotonaldehyde.    The  following
compounds  can  be  detected  using   system   B  and   temperature
program B:  p-, m-, and  o-cresol.
2.    Summary.

     A  portion of  a  sample  is  injected  directly  onto  a   ges
ehromatograph  capillary  column.    The  gas  chromatograph   is
temperature programmed "to  separate  the  constituents  which   are
then detected by a flame ioniaation detector.
3.    Instrumentation and Apparatus.

     3.1.    Gas ehromatograph -- Hewlett-Packard  5880 with auto-
            sampler and  integrator.   Oven temperature profile A
            programmed as  hold  8 min at  50'C,  then  to  220°C at
            8 "C/in in and  hold  5  min.   Program  B:   hold  5 oin at
            50°C then to 25Q"C at 10'C/rain and  hold  15 min.

     3.2.    Column A  —  60 m x  0.32 mm  ID,  0.25  ym film SUPEL-
            COWAX 10  fused  silica  capillary column'.  Set linear
            velocity to 25 cni/sec, Ke, at iOO'C (flow rate =  1.2
            ml/min } .

            Column B -- 30 m x 0.318 mm ID, 0.25  urn  film SE  - 54
            fused silica capillary column.   Set linear velocity
                              B-7

-------
            to  25  cm/sec,  He,  a*  100*0  (flow  rate
     3.3.   Injector  --  configure  for sample splitting  and  ad-
            just'  ratio  to  100:1,    Set  heater  temperature  to
            200'C.

     3.4.   Detector  --   Hewlett-Packard  flame  ionization  de-
            tector.   Hydrogen  flow set at 40 ml/min.   Air flow
            set at 400 ml/sin.  Set sensitivity at 2*2 and ad-
            just  if  necessary.    Set  heater  temperature   to
            25C'C.

     3.5.   Syringes -- 1 ml, 100  ul,  and 10  yl  gas-tight  glass
            for diluting and for sample transfer.
4.    Reagents.

     4.1.   Reagent Water -- prepare with Corning Mega-Pure  dis-
            tillation  system   and  filter   through   activated
            charcoal prior to use.

     4.2.   Methylene Chloride -- J. T.  Baker "Resi-analyaed"  or
            equivalent.

     4.3*   Standard Solution -- prepare "by adding pure  material
            to  water.  Pure material should "be assayed  reference
            liquid such as  Chera  Serve reagents.   If not immedi-
            ately available, supplied compound may be used.

     4,3.1.  Place about  9 ml  of  solvent into a stoppered 10  nil
            flask.   Weigh  the flask.   Add one or two  drops  of
            pure  material to the flask  and reweigh.   Dilute  to
                             B-8

-------
            volume,  mix  well,  and  siore   In  a  teflon-sealed
            screw-eao vial at 4 ° C .
5 .   Calibration.

     '5.1.   External  Standard  Calibration  --  Prepare  working
            standards to bracket the concentration range,  of the
            samples of interest.  Working standards are prepared
            by  diluting  the  standard  solution   with  water  or
            raethylene  chloride  if  the  samples   are  corn  oil
            based.  Analyze according  to  procedure section then
            calculate response factors using this equation:

                            concentration of standard
                                area of standard

            If  the  response  factors  are  constant  over  the
            working range (10/5 Relative  Percent  Difference),  an
            average  response  factor  may  be  used  for  calcu-
            lations .
6.    Quality Control.

     6.1.   Interference -- a water blank  must  be  run  with each
            test to  check for  system contamination.   A  blank
            should  also be  run  between samples of  high  concen-
            tration .

     6.2    Purity  -- reagents used in the  procedure should also
            be  analyzed  with  each  test   to  determine   their
            purity,
                              B-9

-------
     6,3    Spikes --  sample  matrixes  should be spiked svith ihe
            compounds of interest  and  a  percent recovery  calcu-
            lated to access matrix effects and method, accuracy.

     6.4.   Duplicates  --  Some  samples  should  be  analysed  in
            duplicate and  a  relative  percent  difference  calcu-
            lated to access method precision.
7 ,   Procedure.

     7.1.   Calibration as in section 5.

     7.2,   Sample Preparation -- allow samples to  come  to  room
            temperature before handling. , Dilute if necessary to
            bring concentrations within system  working  range  by
            adding portion  of sample  to  water or  to  methylene
            chloride  if corn oil based.

     7.3-   Analysis  -- introduce sample by direct  injection  of
            1 -  2  yl into  the  GO  injection port and begin  the
            temperature program.

     7.4    Identification  -- as  the  compounds  are   analyzed
            individually,  there  should be  no  coelution  inter-
            ferences.   Retention time  should  still be  checked
            against the standard.
3 .    Calculation.

     8,1.    Concentration --  calculate  using peak  area  and  RF
            determined in section 5.1.
                              B-10

-------
5,2.   Dilution -- take into account any dilution performed
       on the sanple or the standard.

8.3    Report  results  in  mg/ml  without  correction  for
       recovery percentage.
                       B-ll

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                                  Study No. 5221.06
          APPENDIX C



CLINICAL PATHOLOGY METHODOLOGY
             C-l

-------

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                                  HEMATOICGY

 Hemoglobin

      Cyanmethejitoglobin method
           Baker Cell  Counter
           Hematorcgy  Series  7000

 Hematocrit

      Indirect method;  calculated value based on erythrocyte
      count and  mean corpuscular volume
           Baker Cell  Counter
           Hematology  Series  7000

 Eryttoocyte Count

      Electronic Counting Procedure
           Baker Cell  Counter
           Hematology  Series  7000

Mean  Corpuscular Volume fMCVl

      Electronic Sizing Procedure
           Baker Cell Counter
          Heniatology Series  7000

Mean  Corpuscular Hemoglobin  fMCH)

      Indirect method;  calculated value based on erythrocyte
     count and hemoglobin
          Baker Cell Counter
          Hematology Series 7000

Mean Corpuscular Hemoglobin Concentration MCHC)

     Indirect method; calculated value based on hematocrit
     and hemoglobin
          Baker  Cell Counter
          Hematology Series 7000

Leukocyte Count

     Electronic Counting Procedure
          Baker Cell Counter
          Hemtology Series 7000
                                    C-2

-------

-------
 Leukocyte Differential Count

      Neutrophils - Immature (bands)
      Neutroph'ils - Mature (segs)
      Mbnocytes
      Easophils
      Lymphocytes ,"
      Ecsinophils
      Wright stain procedure
           Schaljn, O.w. ,  Jain,  N.c.  and Carroll,  E.J.
           Veterinary Hematology,  Color Plates Chapter,
           3rd Edition,  Lee and Feblger,  1975.

              Count
      New methylene blue staining procedure
           Brecher,  G,    Am.  J.  din.  Path.  19,
           895,  1949.

ProthrcsT'bin Time (FT)

      Rate  of change in  absorbance due to clot formation
           Coag-A-Mate

Activated.  Partial_Thrgmboplastiri Time (AFTT)

      Rate  of change in  absorbance due to clot formation
           Coag-A-Mate
                              CT.THICAL CHEMISTRY

Creatinine

     Jaffa's alkaline picrate reaction
          Centrifichem Centrifugal Analyzer System
          Fabiny, D.L. and Ertingshausen, G.
          Clin. Chera., 12, 696, 1971.


Ino_rganic_Phosphorus

     Phosphomolybdate reaction
          Centrifichem Centrifugal Analyzer System
          Daly, J.A.,  and Ertinghausen, G.
          Clin, Chem., 18, 263, 1972.
                                   C-3

-------
 Glucose

      Hexokinase method'
           Centrifichem Centrifugal Analyzer System
           Bcndar, J.L. and. Mead, D.C.
           Clin. Chan. 20, 586, 1974.

 Urea Nitrogen  (BUN)

      Modified urease technique
           Centrifichem Centrifugal Analyzer System
           Talke, H. and Schubert, G.E.
           Klin. Wchnschr. 43, 174, 1965.
      Biuret technique
           Centrifichem Centrifugal Analyzer System
           Kingsley,  G.R. ,  J. Biol. Chem.  131,  197, 1939.

 Albumin

      Brcmocresol Green method
           Centrifichem Centrifugal Analyzer System
           Doumas,  B.T.  and Biggs,  E.G.
           Standard Methods of Clinical  Chemistry,  7,  175,  1972,

 Globulin

      Total Protein - Albumin = Globulin (Calculated value) .

 Calcium.

      Modified alizarin  procedure
           Centrifichem  Centrifugal Analyzer System
           Frings,  C.S., et.  al., Clin.  Chem. ,  16,  816,  1970.

Aspartate Amino Transferase  (AST/SCOT)

     Modified Karmen procedure
          Centrifichem  Centrifugal Analyzer System
          Bergmeyer,  H.V. , Scheibe, P., and Wahlefeld, A.W.
          Clin. Chem.,  24, 58,  1978.

Alanine Ami-no_Transferase  (AUT/SGPT)

     Modified Henley &  Pollard procedure
          Centrifichem  Centrifugal Analyzer System
          Bergmeyer,  H.V. , Scheibe, P., and Wahlefeld, A.W.
          Clin. Chem.,  24, 58,  1978.
                                   C-4

-------
Alkaline  Phosphatase

     Modified  Bowers-McComb procedure
          Centrifiehem Centrifugal Analyzer System
          Bowers, Jr.,  G.N., McComb,  R.3.
          Clin. Chem,,  12,  70,  1966.

Cholesterol

     Allain enzymatic  procedure
          Centrifichem Centrifugal Analyzer System
          Allain, C.C., et.  al., Clin. Chem. 20, 470,  1974.

Total, Bilirubin

     Diazo colorimetrie procedure
          Centrifichem Centrifugal Analyzer System
          Ertinghausen, G.,  Fabiny-Byrd, D.L., Tiffany, T.O.,
          and  Carey, S.J.,  Clin. Chem. JL9,  1366, 1973.

Direct Bilirubin

     Diazo colorimetric procedure
          Centrifichem Centrifugal Analyzer System
          Ertinghausen, G.,  Fabiny-Byrd, D.L., Tiffany, T.O.,
          and  Carey, S.J.,  Clin. Chem. 19,  1366, 1973.

Electrolytes (Na+, K4",  Cl~,  C02)

          Ion  specific  electrodes (Metpath,  Inc.)
                                  URINALYSE5

pualitative Measureirients

     pH        Ketones     Urobilinogen

     Protein   Bilirobin

     Glucose   Blood

     Chemstrip 7L - Chemistry Reagent Strips
          BicHDynamdcs/brnc
          Indianapolis, Indiana
                                    C-5

-------
Specifig_ Gravity

     Optical temperature compensated refractometer

Microscopic Evaluation

     Urinary sediment stained with. Sedi-stain am evaluated using the Ames
     Atlas of Urine Sedjjtient, Ames Co., Division Miles Laboratories, Elkhart,
     Indiana.
                                    C-6

-------
                              Study No.  5221.06
      APPENDIX D




INDIVIDUAL ANIMAL DATA
         D-l

-------

-------
                                                                                                             Study No. 5221.06
                                            DISPOSITION OF ANIHALS IN 13-WEEK ORTHO-CRESOL STUDY IN SPRAGUE DAWLEY RATS
Pi
Dose Level
(mg/kg/day)
0
50
175
600
0
50
175
600
Sex
H
M
H
H
f
F
F
F
Unscheduled Sacrifice3
9/27/85
2911-2913
2944-2946
2977-2979
3010-3012b
3043-3045
3076-3078
3109-3111
3142-3144b
45 -Day Sacrifice
10/31/85, 11/1/B5
2881-2890
2914-2923
2947-2956
2980-2989°
3013-3022
3046-3055
3079-3088
3112-3121°
90-Day Sacrifice
12/16 - 12/18/85
2891-2910
2924-2943
2957-2976
2990-3009d
3023-3042
3056-3075
3089-3108
3122-3141d
                                 8  Initially to be used for neurotoxic  testing, but  this phase eliminated  from study.

                                 b  Early  deaths,  animal numbers 3010, 3012, 3143.

                                 c  Early  deaths,  animal numbers 2984, 3112, 3113, 3121.

                                 d  Early  deaths,  animal numbers 2992, 2993, 2995, 2997, 3000, 3D04, 3006,  3008, 3122-3129, 3131-3134,
                                   3137,  3138, 3140,  3141.

-------

-------
                                                       Study No. 5221,06
                     SUBCHRONIC TOXECITY OF OHmO-CRESOL
                            IN SERAGUE DftKLSY RAIS

                              ABHSEVIMION CODES
Body Weights and Food Consumption

ISAC - interim sacrifice
na   - no data available
dead - unscheduled death

OrganWeights

na   - no data available
dead - unscheduled death
tbw  - terminal body weight

Urinalysis

c    -  clear
cl   -  cloudy
hz   -  hazy
y    -  yellow
py   -  pale yellow
ly   -  light yellow
a    -  amber
dy   -  dark yellow
s    -  straw color
tp   -  triple phosphate
co   -  calcium oxalate
ap   -  amorphous phosphate
n    -  none
tr   -  trace
m    -  aany
f    -  few
ng   -  negative
nr   -  normal
mod  -  moderate
nura  - 'numerous

Hematology & Clinical Chemistry

QNS  - quantity not sufficient
dead - unscheduled death
z    - no clot was formed
thy./para. - thyroid/parathyroid
rt         - right
1ft        - left
occ       -  occasional
>         -  greater than
dead      -  unscheduled death
app       -  appearance
vol       -  volume
uro       -  urcibilinogen
bili      -  bilirubin
ery       -  erytiirocyfces
KBC/HPF   -  number of red blood cells
               under high power field
WBC/HPF   -  number of white blood cells
               under high power field
Casts/tPF -  number of casts under low
               power field
EPI/HPF   -  number of epithelial cells
               cells under high power
               field
                                       D-2

-------

-------
           SU8CHRONIC TOX1CITY OF  ORTHO-CRESOL  IN SPRAGUE DAWlEY RATS
                            HALE BODY  WEIGHT DATA (g>
 DOSE LEVEL
 0 mg/kg/day
                ANIMAL NO.  WEEK 1   UEEK  2  WEEK 3  UEEK 4  WEEK 5  WEEK 6  UEEK 7
50 mg/kg/day
2881
2B82
2883
2884
2885
2B86
2887
2B88
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
220
216
227
216
235
236
220
222
226
214
230
213
217
208
230
225
226
213
228
205
225
245
213
228
205
225
245
215
233
222
216
230
217
233
210
223
223
215
214
234
237
202
218
215
223
227
274
269
283
285
300
294
289
263
280
265
291
268
283
265
293
283
284
293
259
309
290
288
277
293
269
285
311
277
268
273
278
296
276
294
270
288
280
286
275
300
305
266
276
275
287
289
311
316
317
336
343
334
332
295
325
297
327
299
322
308
333
326
333
336
294
370
337
335
318
328
307
327
354
326
336
311
325
340
321
342
307
333
331
330
321
344
349
323
313
310
340
325
318
320
338
344
365
344
345
305
331
307
340
310
334
310
346
350
348
355
305
385
348
351
333
344
322
339
369
338
350
317
357
319
329
338
353
354
350
350
332
361
363
339
331
320
355
343
350
363
387
392
410
376
388
348
374
352
378
346
346
353
384
391
391
400
340
439
388
394
374
387
364
371
412
383
397
353
404
360
372
379
401
387
386
397
369
390
400
381
358
346
404
384
364
384
408
412
426
395
412
357
392
366
396
363
382
373
402
413
4 09
418
356
463
407
410
388
402
390
396
433
404
413
367
424
377
390
409
419
411
410
426
392
418
418
409
378
366
425
404
391
394
441
443
456
425
449
396
426
398
437
382
422
399
435
446
451
452
391
495
448
442
422
433
429
434
482
445
441
392
458
418
423
441
451
449
450
469
420
456
448
458
410
397
452
439
                                        D-3

-------
          SU6CHRONIC TOXICITt OF ORTHO-CRESOL  [N SPRAGUE DAWLEY RATS
                           MALE BODY WEIGHT DATA Cg)
               ANIMAL  NO.   WEEK 1  WEEK 2  WEEK 3  WEEK 4  WEEK 5  WEEK 6  WEEK 7
DOSE
50 rng/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
219
210
215
210
209
223
245
223
219
226
226
235
230
232
203
214
228
235
219
236
220
215
229
221
212
229
220
224
194
229
235
210
215
212
216
209
217
225
203
225
226
215
214
225
273
271
274
263
262
237
316
2S4
276
293
290
3Q2
295
297
243
267
282
236
273
303
279
273
280
276
264
285
258
275
231
282
287
252
252
256
264
260
272
284
- 242
284
285
266
254
276
298
318
320
316
300
350
367
326
309
327
328
351
345
346
287
312
331
340
325
368
329
329
324
324
311
339
290
303
275
333
362
304
305
301
315
312
332
336
281
346
339
313
301
313
313
329
339
318
317
360
389
341
322
341
345
375
359
363
291
323
342
359
333
384
349
342
343
343
327
362
299
336
290
338
384
318
320
311
322
324
344
355
248
373
359
332
322
320
341
371 .
384
369
348
412
432
384
372
375
382
428
406
411
328
379
386
404
374
419
395
383
385
397
372
404
333
390
343
380
428
358
363
348
359
372
389
408
326
411
386
366
364
354
360
394
402
382
375
443
458
402
391
398
411
449
424
423
249
402
415
425
385
445
426
403
407
421
392
432
351
413
368
398
453
383
388
368
387
393
411
439
348
434.
427
383
383
373
385
430
438
417
410
443
493
428
422
431
446
474
459
460
375
431
447
460
416
483
476
441
442
470
423
469
374
448
410
430
492
419
425
392
415
422
444
482
375
474
470
416
396
397
                                       D-4

-------
           SUBCHRON1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE  DAHLEY  RATS
                            MALE BODY WEIGHT DATA (g)
                ANIMAL NO.  WEEK 1   WEEK 2  UEEIC 3  UEEK 4  WEEK  5  WEEK 6  WEEK 7
 DOSE LEVEL;
600 mg/kg/day
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
214
226
211
227
218
226
216
216
224
216
244
240
215
224
219
220
220
218
215
213
222
231
227
224
218
219
218
231
217
215
245
280
258
270
270
267
248
239
263
246
291
291
dead
272
260
262
253
256
254
264
250
279
272
266
dead
26G
270
275
261
260
277
301
302
308
295
301
285
296
300
283
344
335
dead
dead
312
294
293
290
308
290
291
323
325
312
dead
309
313
314
dead
298
286-
308
319
316
dead
316
290
310
306
294
350
341
dead
dead
323
306
286
293
315
300
305
335
330
328
dead
316
325
318
dead
300
332
343
362
347
dead
350
317
344
341
325
394
370
dead
dead
366
341
322
dead
357
338
335
375
372
369
dead
358
343
353
dead
301
356
347
378
361
dead
367
329
359
258
322
418
383
dead
dead
383
356
336
dead
379
351
349
389
389
386
dead
373
363
370
dead
330
382
359
399
386
dead
407
362
394
384
334
445
413
dead
dead
410
dead
360
dead
416
375
380
385
428
423
dead
408
377
401
dead
360
                                       D-5

-------
           SU8CHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                         KALE BODY WEIGHT DATA (g)
DOSE LEVEL
             ANIMAL NO.  'WEEK 8  UEEK 9  WEEK 10  WEEK 11  WEEK 12  WEEK 13  WEEK 14
0 mg/kg/day _- 2881
-" 2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
29130
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
416
418
453
463
477
439
471
414
434
410
453
396
443
417
459
466
485
474
425
515
451
463
450
462
452
455
502
458
461
413
408
434
352
380
371
472
462
482
426
474
469
470
442
408
474
466
na
na
na
na
na
na
na
na
na
na
476
416
460
442
474
498
502
496
441
554
485
482
467
477
471
473
531
480
478
417
na
na
na
na
na
na
na
na
na
na
486
503
448
434
496
479
na
na
na
na
na
na
na
na
na
na
496
430
475
455
490
508
511
521
456
574
507
504
477
488
485
489
552
500
492
445
na
na
na
na
na
na
na
na
na
na
500
532
472
448
516
494
na
na
na
na
na
na
na
na
na
na
469
412
471
465
501
489
506
513
464
576
479
494
474
507
490
461
534
507
494
463
na
na
na
na
na
na
na
na
na
na
478
529
473
449
521
473
na
na
na
na
na
na
na
na
ne
na
502
447
502
472
514
526
544
544
479
609
505
525
504
533
518
503
549
493
472
473
na
na
na
na
na
na
na
na
na
na
512
537
505
466
545
510
na
na
na
na
na
na
na
na
na
na
526
451
521
491
523
543
559
563
492
627
540
552
523
549
533
524
575
527
501
489
na
na
na
na
na
na
na
na
na
na
525
531
532
481
557
539
na .
na
n3
na
na
na
na
na
na
na
548
463
533
502
533
558
569
578
502
648
562
567
538
564
549
542
601
559
518
499
na
na
na
na
na
na
na
na
na
na
538
602
543
498
576
553
na  =  no  data  available.
                                  D-6

-------
           SUBCHRONIC TOXICITY Of CRTHD-CRESOL IN SPRAGU6 OAULEY RATS
                         MALE SOOT WEIGHT DATA (g)
             ANIMAL NO.  WEEK 8  WEEK 9  WEEK 10  WEEK 11  WEEK 12 WEEK 13  WEEK 14
DOSE LEVEL
50 mg/kg/day 2930
• (continued) .-" 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
405
463
462
446
433
513
527
455
442
444
472
494
481
496
375
457
48Q
492
439
497
501
449
443
496
442
506
400
477
435
450
507
445
452
410
435
447
478
506
395
504
500
440
423
413
418
436
475
466
450
543
541
477
462
468
488
515
504
520
na
na
na
na
na
na
na
na
na
na
465
520
422
504
464
472
523
462
471
425
450
469
510
542
418
522
525
454
455
431
429
504
504
480
426
558
558
493
477
478
514
542
520
541
na
na
na
na
na
na
na
na
na
na
496
543
425
516
498
489
554
478
492
444
469
499
518
568
467
551
547
424
475
446
423
497
510
503
422
546
559
499
487
451
505
553
529
556
na
na
na
na
na
na
na
na
na
na
513
572
444
543
526
512
585
502
517
465
482
524
545
589
459
577
588
476
485
457
445
520
.533
521
466
591
582
524
511
496
543
574
545
574
na
na
na
na
na
na
na
na
na
na
530
587
463
558
553
521
621
522
542
488
502
542
572
614
481
602
597
503
480
475
455
541
558
539
460
601
602
536
512
511
555
594
561
595
na
na
na
na
na
na
na
na
na
na
548
614
478
582
570
534
629
523
555
501
513
554
592
627
493
624
611
516
490
481
467
557
567
554
472
621
619
547
524
510
581
613
581
609
na
na
na
na
na
na
na
na
na
na
557
616
501
605
578
549
651
545
567
514
522
569
603
650
503
627
631
527
507
492
  na  =  no  data  available.
                                   D-7

-------
           SUBCHRON1C TOXICITY Of ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
                          MALE 3QOY WEIGHT DATA (g)
              ANIMAL NO.  WEEK 8  WEEK 9  WEEK 10  UEEK  11  WEEK 12  WEEK 13 WEEK 14
DOSE LEVEL
600 mg/kg/day 2980
r 2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2994
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
403
380
403
407
dead
406
376
404
412
334
466
437
dead
dead
436
dead
379
dead
433
393
385
391
440
436
dead
412
393
419
dead
388
na
na
na
na
dead
na
na
na
na
na
490
464
dead
dead
469
dead
393
dead
459
402
412
422
470
440
dead
427
dead
432
dead
373
na
na
na
na
dead
na
na
na
na
na
508
478
dead
dead
495
dead
404
dead
474
410
429
448
472
474
dead
409
dead
335
dead
393
na
na
na
na
dead
na
na
na
na
na
527
493
dead
dead
515
dead
421
dead
485
415
dead
368
498
493
dead
442
dead
415
dead
412
na
na
na
na
dead
na
na
na
na
na
546
512
dead
dead
544
dead
439
dead
503
430
dead
426
525
512
dead
469
dead
455
dead
435
na
na
na
na
dead
na
na
na
na
na
561
520
dead
dead -
558
dead
447
dead
511
441
dead
449
543
525
dead
488
dead
487
dead
446
na
na
na
na
dead
na
na
na
na
na
566
531
dead
dead
581
dead
453
dead
524
453
dead
481
557
541
dead
511
dead
517
dead
456
na = no  data available.
                                   D-a

-------
           SU8CHROMSC TOXICITY OF ORTHO-CRESOL  IN  SP8AGUE DAULEY RATS
                      '   MALE BODY WEIGHT  CAIN  DATA  Cg)
                ANIMAL NO.   WEEK 1   WEEK 2   WEEK 3  MEEK 4  WEEK 5  WEEK 6  WEEK 7
 DOSE LEVEL
 0 mg/kg/day
50 ng/kg/day
2881
2882
2883
2884
2885
2886
288?
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
54
53
56
69
65
58
69
41
54
51
61
55
66
57
63
58
58
80
31
104
65
43
64
65
64
60
66
62
35
51
62
66
59
61
60
65
57
71
61
66
68
64
58
60
64
62
91
100
90
120
108
93
112
73
99
83
97
86
105
100
103
101
107
123
66
165
112
90
105
100
102
102
109
111
103
89
109
110
104
109
97
110
108
115
107
110,
112
121
95
95
117
98
98
104
111
128
130
ioa
125
83
105
93
110
97
117
102
116
125
122
142
77
180
123
106
120
116
117
114
124
123
117
95
141
89
112
105
143
131
127
135
118
127
126
137
113
105
132
116
130
147
160
176
175
140
168
126
148
138
148
133
129
145
154
166
165
187
112
234
163
149
161
159
159
146
167
163
164
131
188
130
155
146
191
164
163
182
155
156
163
179
140
131
18T
157
144
168
181
196
191
159
192
135
166
152
166
150
165
165
172
188
183
205
128
258
182
165
175
174
185
171
188
189
180
145
208
147
173
176
209
188
187
211
178
184
181
207
160
151
202
177
171
178
214
227
221
189
229
174
200
184
207
169
205
191
205
221
225
239
163
290
223
197
209
205
224
209
237
230
208
170
242
188
206
208
241
226
227
254
206
222
211
256
192
182
229
212
196
202
226
247
242
203
251
192
208
196
223
183
226
209
229
241
259
261
197
310
226
218
237
234
247
230
257
243
228
191
192
204
135
147
161
249
239
267
212
240
232
268
224
193
251
239
                                        D-9

-------
          SUBCHRON1C  TOX1C1TY OF ORTHO-CRESOL IN SPRAGUE OAULEY RATS
                     '  MALE SOOY WEIGHT GAIN DATA (g)
               ANIMAL NO.  WEEK 1  WEEK 2  WEEK 3  WEEK 4  WEEK 5  WEEK 6  WEEK 7
DOSE LEVEL
50 mg/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/diy 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
54
61
59
53
53
9
71
61
57
67
64
67
65
65
35
53
54
51
54
67
59
58
51
55
52
56
38
51
37
53
52
42
37
44
48
51
55
59
39
59
59
51
40
51
79
108
105
106
91
122
122
103
90
101
102
116
115
114
79
98
103
105
106
132
109
114
95
103
99
110
70
79
81
104
127
94
90
89
99
103
115
111
78
121
113
98
87
88
94
119
124
108
108
132
144
118
103
115
119
140
129
131
83
114
114
124
114
148
129
127
114
122
115
133
79
112
96
109
149
108
105
99
106
115
127
130
45
148
133
117
108
95
122
161
169
159
139
184
187
161
153
149
156
193
176
179
120
165
158
169
155
183
175
168
156
176
160
175
113
166
149
151
193
148
148
136
143
163
172
183
123
186
160
151
150
129
141
184
187
172
166
215
213
179
172
172
185
214
194
196
41
188
187
190
166
209
206
193
178
200
180
203
131
189
174
169
218
173
173
156
171
184
194
214
145
209
201
168
169
148
166
220
223
207
201
215
248
205
203
205
220
239
229
228
167
217
219
225
197
247
256
226
213
249
211
240
154
224
216
201
257
209
210
180
199
213
227
257
172
249
244
201
182
172
186
253
247
236
224
285
282
232
223
218
246
259
251
264
167
243
252
257
220
261
281
234
214
275
230
277
180
253
241
221
272
235
237
198
219
233
261
281
192
279
274
225
209
188
                                      D-10

-------
          SUSCHRQNIC TQXICI1Y OF ORTHO-CRESOL IN SPRAGUE DAHL6Y  RATS
                   '   MALE BOOT WEIGHT GAIN DATA 
-------
       SUSCHRONIC TOX1C1TY OF ORTHO-CRESOL  IN SPRAGUE DAWLEY RATS
                   'MALE BODY WEIGHT GAIN DATA eg)
             ANIMAL HO.   WEEK 8 WEEK 9 WEEK 10  WEEK 11  WEEK 12  WEEK 13
DOSE LEVEL
0 mg/kg/diy 2381
2882
2883
2384
2885
2886
2887
2888
28B9
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
na
ne
na
na
na
na
na
na
na
na
246
203
243
234
244
273
276
283
213
349
260
237
254
249
266
248
286
265
245
195
na
na
na
na
na
na
na
na
na
na
249
301
230
219
273
252
na
na
na
na
na
na
na
na
na
na
266
217
258
247
260
283
285
308
228
369
232
259
264
260
230
264
307
285,
259
223
na
na
na
na
na
na
na
na
na
na
263
330
254
233
293
267
na
na
na
na
na
na
na
na
na
na
239
199
254
257
271
264
280
300
236
371
254
249
261
279
285
236
289
292
261
241
na
na
na
na
na
na
na
na
na
na
241
327
255
234
298
246
na
na
na
na
na
na
na
na
na
na
272
234
285
264
284
301
318
331
251
404
280
280
291
305
313
273
304
278
239
251
na
na
na
na
na
na
na
na
na
na
275
335
287
251
322
283
na
na
na
na
na
na
na
na
na
na
296
238
304
283
293
318
333
350
264
422
315
307
310
321
328
299
330
312
268
267
na
na
na
na
na
na
na
na
na
na
288
379
314
266
334
312
na
na
na
na
na
na
na
na
na
na
318
250
316
294
303
333
343
365
274
443
337
322
325
336
344
317
356
344
285
277
na
na
na
na
na
na
na
na
na
na
301
400
325
283
353
326
na = no  data  available.
                                D-12

-------
       SUBCHRONIC TOXICITt OF QRTHO-CRESOl  IN SPRAGUE OAUIEY RATS
                  'NALE BODY UEIGHT GAIN  DATA 
-------
    SUBCHRONIC TOXICITT OF ORTHQ-CRESOL IN SPRAGUE DAWLEY RATS
               ' MALE BODY UEIGHT GAIN DATA (g)
          ANIMAL NO.  WEEK 8  WEEK 9 WEEK 10  UEEK 11  WEEK 12  WEEK  13
DOSE LEVEL
600 mg/kg/day 2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
.3005
3006
3007
3008
3009
ns
na
na
na
na
na
na
na
na
na
246
224
na
na
250
na
173
na
244
1B9
190
191
243
236
na
208
na
201
na
158
na
na
na
na
na
na
na
na
na
na
264
238
na
na
276
na
184
na
259
197
207
217
245
250
na
190
na
104
na
178
na
na
na
na
na
na
na
na
na
na
283
253
na
na
296
na
201
na
270
202
na
137
271
269
na
223
na
184
na
197
.na
na
na
na
na
na
na
na
na
na
302
272
na
na
325
na
219
na
283
217
na
195
298
283
na
250
na
224
na
220
na
na
na
na
na
na
na
na
na
na
317
280
na
na
339
na
227
na
296
228
na
218
316
301
na
269
na
256
na
231
na
na
na
na
na
na
na
na
na
na
322
291
na
na
362
na
233
na
309
239
na
250
330
317
na
292
na
ZB6
na
241
na = no  data  available,
                               D-14

-------
           SUBCHRONIC icxicm OF  ORTHQ-CRESOI IN SPRAGUE DAULEY RATS
                           FEMALE  BODf WEIGHT DATA (g)
 DOSE LEVEL.
 0 mg/kg/day
                ANIMAL  NO.  WEEK  1  WEEK 2  WEEK 3  WEEK 4  WEEK 5   WEEK 6  UEEK 7
50 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
30Z5
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
161
156
144
163
170
171
155
150
164
153
164
147
165
152
158
155
157
164
154
155
153
153
153
155
162
138
142
153
141
156
158
162
147
164
161
160
157
149
152
167
151
163
176
161
151
159
178
177
166
188
200
190
176
168
188
171
177
171
181
175
190
169
177
185
176
175
166
171
170
171
182
151
163
169
165
177
178
184
172
188
139
177
179
173
163
192
166
196
202
177
166
177
204
198
183
213
229
215
198
191
207
189
202
197
218
191
216
196
199
204
188
192
184
188
190
194
195
177
208
190
187
196
194
209
192
206
211
193
205
188
178
215
185
214
237
197
182
203
202
200
182
217
238
215
202
200
202
198
208
198
222
197
219
199
205
208
196
189
195
195
193
188
202
203
178
208
194
186
198
209
200
212
220
194
207
194
184
220
189
224
238
197
184
207
230
220
197
242
260
231
215
203
223
211
230
217
244
214
232
222
224
228
215
212
208
210
208
214
224
203
222
222
204
213
222
226
220
233
240
216
228
215
198
250
203
234
262
223
204
227
235
230
201
241
268
225
227
215
229
212
224
221
246
203
246
217
227
225
217
210
207
214
208
220
222
205
221
218
210
212
225
236
232
240
248
217
229
218
201
249
210
247
264
224
205
237
249
242
212
260
280
256 .
242
230
243
221
237
238
268
218
258
234
249
238
232
227
221
230
222
236
227
239
23Q
230
230
223
235
249
245
243
251
233
244
234
211
263
222
262
282
238
220
254
                                       D-15

-------
     SUBCHRQNIC TOXICITY OF ORTHO-CRESOL JN SPRftGUE DAULEr RATS
                 FEMALE iOOY WEIGHT DATA (g)
         AMIMAL NO.  UEEK 1  WEEK 2  WEEK 3  WEEK 4  WEEK 5  UEEK 6 UEEK 7
50 mgAg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 ing/ kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
169
157
153
162
156
166
145
153
160
166
154
156
149
156
163
149
183
150
159
155
148
149
147
157
155
162
145
158
151
153
na
160
141
150
167
170
158
166
155
156
170
161
149
167
183
180
174
190
179
183
164
178
184
194
180
174
173
184
186
174
212
166
183
171
174
164
166
183
172
176
171
185
177
177
166
188
161
169
189
202
178
189
158
182
193
183
168
198
216
202
195
216
202
215
183
204
206
217
202
198
189
205
209
203
241
188
211
193
193
184
181
209
195
193
191
209
197
199
181
207
183
193
207
229
194
208
189
205
225
207
179
217
213
210
196
221
208
220
189
217
217
218
211
199
194
212
215
204
248
189
208
204
190
186
186
207
199
198
193
214
203
206
182
22D
1B4
193
209
232
203
210
196
207
231
213
176
220
230
229
216
243
221
241
204
244
236
245
224
218
213
238
234
224
272
210
227
216
208
206
198
226
226
210
200
234
226
232
198
223
200
213
220
262
229
237
207
224
254
230
' 159
232
244
236
223
252
223
251
206
255
248
255
235
223
218
na
237
235
281
215
232
224
211
211
207
237
232
214
216
245
234
231
200
231
207
216
235
265
238
242
208
233
255
237
190
247
267
254
236
276
246
266
215
266
255
272
246
230
236
264
246
248
292
224
252
236
229
228
214
240
244
216
225
259
248
250
212
236
216
224
245
282
252
251
224
257
262
263
210
256
na  = no data available; body  weights inadvertently
      not recorded,
                            D-16

-------
           SUBCHRONIC TCXIC1TY  OF  ORTHO-CRESOl  IN SPRAGUE DAWLEY RATS
                           FEMALE  BODY WEIGHT DATA Cg)
                ANIMAL MO.   UE£K  1  WEEK 2  WEEK 3  WEEK 4  WEhK 5  WEEK 6  WEEK  7
 DOSE LEVEt
600 mg/kg/day
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
161
127
143
161
145
170
141
152
157
155
156
154
161
160
152
156
160
158
155
138
156
146
138
158
146
163
162
166
138
177
174
151
169
132
160
190
159
177
173
dead
172
169
179
170
170
dead
181
180
162
154
179
159
158
176
163
183
173
186
148
202
193
168
195
201
185
214
176
198
197
dead
194
190
201
184
199
.dead
194
206
190
172
192
dead
179
191
181
dead
dead
208
166
224
dead
176
199
207
189
220
176
201
198
dead
196
188
203
, 186
200
dead
198
209
189
dead
dead
dead
dead
198
185
dead
dead
211
171
222
dead
185
209
216
202
242
193
209
207
dead
dead
dead
226
201
216
dead
210
244
208
dead
dead
dead
dead
209
201
dead
dead
232
dead
255
dead
196
222
232
208
227
204
214
215
dead
dead
dead
224
209
218
dead
211
255
218
dead
dead
dead
dead
215
208
dead
dead
231
dead
258
dead
dead
230
235
222
259
212
215
220
dead
dead
dead
dead
dead
dead
dead
224
256
226
dead
dead
dead
dead
216
219
dead
dead
240
dead
dead
                                        D-17

-------
          SUBCHRQNIC TOXtClTY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
                        FEMALE BCOY WEIGHT DATA (g)
             ANIMAL HO.  WEEK a WEEK 9  WEEK 10  WEEK 11  WEEK 12  WEEK 13  WEEK 14
DOSE LEVEL
0 mg/kg/day 3013.
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
- 3039
3040
3041
3042
50 mg/kg/day 3044
3047
3068
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
253
252
219
262
283
263
248
236
242
213
238
241
272
226
267
241
242
241
237
234
235
239
227
235
240
236
242
237
239
232
237
256
247
263
272
229
2S7
241
217
265
232
273
292
247
222
260
na
na
na
na
na
na
na
na
na
na
245
250
294
234
285
252
262
247
246
242
242
243
240
245
246
246
261
245
247
236
na
na
na
na
na
na
na
na
na
na
243
290
302
264
224
275
na
na
na
na
na
na
na
na
na
na
254
256
298
238
296
253
262
252
255
248
247
240
239
247
254
259
257
247
252
241
na
na
na
na
na
na
na
na
na
na
249
297
307
271
232
283
na
na
na
na
na
na
na
na
na
na
253
E58
305
245
294
263
267
256
265
259
259
250
254
249
260
263
267
264
266
249
na
na
na
na
na
na
na
na
na
na
257
307 '
332
278
239'
287
na
na
na
na
na
na
na
na
na
na
257
267
315
247
310
272
274
263
275
269
258
253
262
254
254
266
271
264
268
241
na
na
na
na
na
na
na
na
na
na
262
315
338
236
246
297
na
na
na
na
na
na
na
na
na
na
255
271
318
251
310
276
269
263
274
273
267
260
257
260
256
273
276
268
263
246
na
na
na
na
na
na
na
na
na
na
266
323
345
284
244
304
na
na
na
na
na
na
na
na
na
na
260
275
320
255
310
279
282
265
274
273
269
266
255
263
266
282
277
275
273
253
na
na
na
na
na
na
na
na
na
na
275
335
347
289
253
309
 na  =  no  data  available.
                                     0-18

-------
           SUBCHRONIC TQXiCiTY OF ORTHO-CRESOL  IK SPRAGUE DAWLEY RATS
                         FEMALE SCOT WEIGHT DATA (g)
             ANIMAL NO.  WEEK 8  WEEK 9  WEEK  10  WEEK 11  WEEK 12  WEEK 13  WEEK t4
DOSE LEVEL
50 mg/kg/day 3062-
(continued) 3063
3064
3065
3066
3067
3063
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3068
3089
309C
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
271
260
245
287
253
278
223
266
269
277
250
236
243
268
249
260
286
226
257
245
238
225
216
248
250
225
231
267
248
255
222
242
227
229
254
292
263
259
230
248
275
208
204
264
290
268
255
297
269
286
232
283
288
289
263
245
259
280
na
na
na
na
na
na
na
na
na
na
261
235
243
275
268
267
227
254
236
240
263
301
268
270
238
259
285
259
217
278
290
274
255
307
272
291
238
305
288
290
268
248
266
292
na
na
na
na
na
na
na
na
na
na
265
241
247
292
269
276
227
260
239
246
274
311
275
275
242
275
299
267
214
281
301
275
264
322
281
304
241
307
293
297
281
260
273
297
na
na
na
na
na
na
na
na
na
na
264
233
248
288
280
277
226
261
253
245
279
309
281
278
248
286
299
269
229
289
318
290
265
333
285
312
244
323
302
305
289
266
281
303
na
na
na
na
na
na
na
na
na
na
274
241
262
302
295
292
239
262
241
245
291
322
290
2S3
263
300
303
281
231
294
313
239
269
339
287
312
249
328
308
309
283
247
280
321
na
na
na
na
na
na
na
na
na
na
276
244
264
309
304
304
247
270
260
251
299
315
290
287
267
302
313
289
234
294
321
289
274
345
291
326
254
336
315
315
293
265
294
325
na
na
na
na
na
na
na
na
na
na
282
252
263
312
303
303
258
275
259
260
304
324
295
289
269
317
311
288
238
294
      na = no  data  available.
                                       0-19

-------
        SUBCHRONIC  TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                      FEMALE BODY WEIGHT DATA (g)
          ANIMAL NO.  WEEK 8  WEEK 9  WEEK 10  WEEK 11  WEEK 12  WEEK 13  WEEK  14
DOSE LEVEL
600 mg/kg/day 3112
31 IT
31H
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
dead
dead
228
236
218
260
207
226
223
dead
dead
dead
dead
dead
dead
dead
224
264
229
dead
dead
died
dead
229
219
dead
dead
249
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
2Z4
272
236
dead
dead
dead
dead
215
225
dead
dead
260
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
234
281
240
dead
dead
dead
dead
233
236
deed
dead
263
dead ,
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
240
287
247
dead
dead
dead -
dead
242
247
dead
dead
271
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
243
296
259
dead
dead
dead
dead
245
254
dead
dead
275
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
257
303
258
dead
dead
dead
dead
247
270
dead
dead
285
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
265
306
256
dead
dead
dead
dead
255
275
dead
dead
284
dead
dead
na = no  data available.
                                    D-20

-------
           SUBCHRONIC  TOXICITY  OF ORTHO-CRESOL  IN SPRACUE DAWIEY RATS
                      '  FEMALE  BODY WEIGHT GAIN DATA (g)
                ANIMAL  NO.   WEEK  1   UEEK  2  WEEK 3  WEEK 4  WEEK 5  WEESC 6  WEEK 7
 DOSE LEVEL:     	
 0 mg/kg/day       3013
                   3014
                   3015
                   3016
                   3017
                   3018
                   3019
                   3020
                   3021
                   3022
                   3023
                   3024
                   3025
                   3026
                   3027
                   3028
                   3029
                   3030
                   3031
                   303Z
                   3033
                   3034
                   3035
                   3036
                   3037
                   3038
                   3039
                   3040
                   3041
                   3042

50 mg/kg/day       3046
                   3047
                   3048
                   3049
                   3050
                   3051
                   3052
                   3053
                   3054
                   3055
                   3056
                   3057
                   3058
                   3059
                   3060
                   3061
17
21
22
25
30
19
21
18
24
18
13
24
16
23
32
14
20
2T
22
20
13
18
17
16
20
13
21
16
24
21
20
22
25
24
28
17
22
24
11
25
15
33
26
16
15
18
43
42
39
50
59
44
43
41
43
36
38
50
53
39
58
41
42
40
34
37
31
35
37
39
33
39
66
37
46
40
36
47
45
42
50
33
48
39
26
48
34
51
61
36
31
44
41
44
38
54
68
44
47
50
38
45
44
51
57
45
61
44
48
44
42
34
42
42
40
33
40
65
36
55
53
30
40
47
53
48
59
34
50
45
32
53
38
61
62
36
33
48
69
64
S3
79
90
60
60
53
59
58
66
70
79
62
74
67
67
64
61
57
55
57
55
59
62
65
80
69
63
57
64
64
73
69
79
56
71
66
46
83
52
71
86
62
53
68
74
74
57
78
98
54
72
65
65
59
60
74
81
56
88
62
70
61
63
55
54
61
55
65
60
67
79
65
69
56
67
74
85
76
87
57
72
69
49
82
59
84
88
63
54
78
88
86
68
97
110
85
87
80
79
68
73
91
103
66
100
79
92
74
78
72
68
77
69
81
65
101
88
77
89
67
77
87
98
84
90
73
87
85
59
96
71
99
106
77
69
95
92
96
75
99
113
92
93
36
78
60
74
94
107
74
109
86
85
77
83
79
82
86
74
80
78
98
100
84
98
76
79
94
100
99
111
69
100
92
65
98
81
110
116
86
71
101
                                        D-21

-------
         SUBCHRONIC  TOXICITY CF QRTHQ-CRESQl  IN SPRAGUE DAWIEY RATS
                   ' FEMALE BODY WEIGHT GAIN DATA Cg)
             AN[HAL NO.  WEEK 1  WEEK 2  WEEK 3  WEEK 4  WEEK 5  WEEK 6  WEEK 7
DOSE LEVEL
50 ing/kg/day 3062
{continued} 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/ kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097.
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
14
23
21
28
23
17
19
25
24
23
26
18
24
28
23
25
29
16
24
16
26
15
19
26
17
14
26
27
26
24
na
28
20
19
22
32
20
23
3
26
23
22
19
31
47
45
42
54
46
49
38
51
46
51
48
42
40
49
46
54
58
38
52
38
45
35
34
52
40
31
46
51
46
46
na
47
42
43
40
59
36
42
34
49
55
46
30
50
49
53
43
59
52
54
44
64
57
52
57
43
45
56
52
55
65
39
49
49
42
37
39
50
44
36
48
56
57
53
na
60
43
43
42
62
45
44
41
51
61
52
27
53
61
72
63
81
65
75
59
91
76
79
70
62
64
82
71
75
89
60
68
61
60
57
51
69
71
48
55
76
75
79
na
63
59
63
53
92
71
71
52
68
64
69
10
65
75
79
70
90
72
85
61
102
88
89
81
67
69
na
74
86
98
65
73
69
70
62
60
80
77
52
71
87
83
78
na
71
66
66
68
95
80
76
53
77
85
76
41
80
98
97
83
114
90
100
70
113
95
106
92
74
87
108
83
99
109
74
93
81
81
79
67
83
89
54
80
101
97
97
na
76
75
74
78
112
94
85
69
101
92
102
61
89
102
103
92
125
97
112
78
113
109
111
96
80
94
112
86
111
103
76
98
90
90
76
69
91
95
63
86
109
97
102
ne
82
86
79
87
122
105
93
75
92
105
47
55
97
     na  =  no  data available.
                                 D-22

-------
      SUBCHRONIC TOXICITT OF QRTHO-CRESQl  IN SPRAGUE DAWLET RATS
                " FEMALE BODY WEIGHT GASH DATA (g)
          AMI HAL NO.  WEEIC 1  WEEK 2  WEEK 3  WEEK 4  UEEK 5  WEEK 6  WEEK 7
600 mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
31Z3
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
13
H4
26
21
15
20
18
25
16
na
16
15
18
10
18
na
21
22
7
16
23
13
20
18
17
20
11
20
10
25
32
41
52
40
40
44
35
46
40
na
38
36
40
24
47
na
34
48
35
34
36
na
41
33
35
na
na
42
28
47
na
49
56
46
44
50
35
49
41
na
40
34
42
26
48
na
38
51
34
na
na
na
na
40
39
na
na
45
33
45
na
58
66
55
57
72
52
57
50
na
na
na
65
41
64
na
50
66
53
na
na
na
na
51
55
na
na
66
na
78
na
69
79
71
63
57
63
62
58
na
na
na
63
49
66
na
51
97
63
na
na
na
na
57
62
na
na
65
na
81
na
na
87
74
77
89
71
63
63
na
na
na
na
na
na
na
64
98
71
na
na
na
na
58
73
na
na
74
na
na
na
na
85
75
73
90
66
74
66
na
na
na
na
na
na
na
64
106
74
na
na
na
na
71
73
na
na
83
na
na
na = no  data  available.
                                D-23

-------
       SU8CHRCNIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY  RATS
                   FEMALE BODY WEIGHT CAIN DATA 
-------
       SU3CHROKIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWLcY RATS
                   FEMALE BOOY WEIGHT GAIN DATA 
-------
    SUBCHROMIC TOXICITY CF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
               FEMALE BODY yElGHT GAIN DATA (g)
          ANIMAL NO.  WEEK 8 WEEK 9 WEEK 10  WEEK 11  WEEK 12  WEEK 13
DOSE LEVEL
600 mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141

na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
64
114
81
na
na
na
na
57
79
na
na
94
na
na

na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
74
123
85
na
na
na
na
75
90
na
na
97
na
na

na
na
na
na
na
na
na
na>
na
na
na
na
na
na
na
na
80
129
92
na
na
na
na
84
101
na
na
105
na
na

na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
83
138
104
na
na
na
na
87
108
na
na
109
na
na

na
na
na
na
na
na
na
na
. na
na
na
na
na
na
na
na
97
145
103
na
na
na
na
89
124
na
na
119
na
na

na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
105
148
101
na
na
na
na
97
129
na
na
118
na
na
na = no  data  available.
                              D-26

-------
            SUBCHROHIC  TOXIC1TY  OF ORTHO-CRESOL  Itt  SPRAGUE 0AWLEY RATS
                        KALE  FOOD CONSUMPTION DATA  (g/day)
                ANIMAL  NO.  week  1   week  2  week  3  week 4  week 5  week 6  week 7
 DOSE  LEVEL
 0 mg/kg/day
50 mg/kg/day
2831
2B82
2883
2384
2685
2886
2387
2B88
2889
2890
2891
2892
2893
2394
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
23.1
22.7
22.1
26.8
25.5
26.2
22.7
20.4
22.4
22.3
24.5
21.4
23.4
21.4
24.3
22.9
22.7
26.8
21.0
28.2
25.1
25.5
21,3
24.9
22.5
24.7
26.8
23.9
22.9
23.5
25.0
25.0
22.3
25.9
22.0
23.0
23.2
23.1
22.6
27.6
23.6
21.3
21.3
22.1
22.8
24.7
33.8
17.7
24.7
30.0
28.2
27.7
26.2
22.8
26.7
23,1
26.3
22.9
25. 9
24.7
27.4
26.7
26.4
16.2
23.5
33.8
28.6
27.3
24.6
26. 8
25.3
28. 5
30.4
26.3
26.4
15.0
25.8
26.6
26.1
29.5
24.0
26.1
28.0
26.5
26.8
31.8
27.9
27.9
24.6
25.0
26.5
27.2
22.2
22.9
24.4
2S.2
25.6
28.3
25.3
20.0
24.8
22.5
24.9
20.5
24.5
21.0
23.8
24.9
25.2
33.6
23.9
34.0
25.4
27.1
22.5
28.6
25.0
27.3
31.0
23.6
18.4
22.4
14.0
22.7
22.3
25.5
25.0
26.0
24.6
26.3
23.8
30.7
24.2
26.6
22.7
21.5
25.3
26.7
16.0
23.9
26.1
28.2
29.8
25.4
25.2
23.5
25.7
23.0
25.3
21.5
20 .B
22.3
24.3
24.7
26.8
28.5
23.1
29.7
25.6
25.9
24.1
25.8
28.0
25.5
30.2
24.4
25.8
25.3
27.0
22.6
22.4
26.6
27.1
23.4
22.3
27.5
25.1
25.1
22.4
25.8
22.3
21.4
25.3
23,9
21.9
23.5
24.7
27.3
25.9
25.9
24.6
22.6
24.8
22.1
25.2
20.3
23.5
21.7
23.3
25.3
26.1
27.7
23.6
31.2
25.2
27.2
24.5
25.3
26.3
27.0
31.7
24.5
24.5
23.4
25.5
23.4
22.8
28.3
27.3
23.7
24.1
27.7
24,4
28.8
23.0
27.3
22.3
20.8
23.8
24.7
22.9
18.8
'24.0
26.6
27.1
26.3
24.7
22.9
26.0
21.4
26.3
2D.6
31.4
22.3
24.2
25.8
28.7
30.1
28.1
33.0
24.2
27.7
E3.6
28.0
25.6
24.7
31.9
28.8
25.3
22.8
21.1
23.3
14.8
16.8
16.1
24.5
23.5
27.4
22.6
26.6
23.8
26.6
25.2
21.3
24.0
25.7
38.7
22.2
18.5
20,3
22.0
18.0
30.2
8.9
17.0
16.8
24.5
17.1
21.1
19.5
22.0
21.1
22.0
25.0
24.3
26.9
21.8
25.5
21.6
25.3
22.8
23.4
28.8
22.1
21.9
23.1
6.6
17.5
3.5
3.9
3.5
17.3
19.9
21.6
16.0
26.4
20.1
23.3
22.1
20.2
20.5
26.5
                                              D-27

-------
          SUBCHRONtC TOXICITY OF ORTHO-CRESOL IN SPRAGUE  DAUIEY  RATS
                      MALE FOOD CONSUMPTION DATA (g/day3
               ANIMAL NO,   week 1   week 2  week 3  heek 4   wsek  5   week 6  week 7
DOSE LEVEL
50 mg/kg/day 2930
(continued) 293f
• 2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
22.6
21.5
21.6
23.5
20,9
25.2
24.4
23.2
24.5
23.1
22,8
25.5
26.0
24.2
18.4
21.5
27.5
22.3
22.5
27.6
22.3
25.6
23.0
21.9
20.5
24.1
21.1
20.8
17.6
22.8
27.9
19.1
22.0
22.3
23.8
21.3
24.6
26.8
21.0
23.7
24.8
19.9
24.5
16.2
23.6
22.8
28.9
26.9
24.6
30.6
29.7
27.1
26.0
25.2
26.7
28.4
30.6
29.3
22.0
26.1
26.3
25.7
24.3
30.9
25.5
25.5
24.6
24.5
24.1
27,6
37.9
22.6
20.8
25.1
27.7
26.8
24.5
24.0
25.3
24.6
26.8
26.0
23.4
28.3
27.2
24.3
24.8
23.3
22.9
24.6
25.9
25.8
22.5
27.5
26.2
25.2
25.3
22.6
22.5
27.3
29.2
26.6
20.6
23.2
25.8
24.7
20.5
28.4
24.9
23.6
22.0
22.0
23.4
28.5
19.8
23.8
20.9
22.6
27.9
22.7
25.4
23.4
22.5
23.5
23.2
26,0
18.2
23.1
26.7
21.8
21.8
19.7
20.7
24.5
25.3
26.0
21.5
27.2
26.0
24.8
27.5
20.9
22.0
28.1
29.6
26,7
21.5
24.5
27.8
26.1
22.9
28.3
29.8
28.2
26.6
29.0
26.5
28.2
22.2
27.8
24.3
24.1
30.3
23.3
27.2
25.0
23.4
25.0
27.8
29.7
22.3
27.2
29.8
25.6
29.8
25.3
21.0
25.3
24.5
24.8
23.4
25.6
24.9
21.5
25. Z
21.5
23.0
25.2
23.4
25.5
22.6
23.9
28.8
24.0
20.8
28.3
28.5
23.6
24.9
28.0
22.3
26.7
21.7
26.6
24.1
23.6
29.6
22.0
25.0
24.2
23.3
23.1
25.3
30.4
22.9
26.1
29.2
21.3
17.1
21.8
21.1
26.6
24.0
'26.1
22.7
29.4
27.0
22.8
24.0
19.2
24.4
24.2
29.1
26.1
21.8
25.0
29.6
27.3
23.4
27.1
28.8
25.6
26.1
30.5
22.1
27.3
23.3
25.8
24.3
24.5
26.5
23.3
27.4
24.2
25.9
24.4
27.9
30.5
24.5
27.6
32.5
21.1
23.1
20.1
17.8
23.9
21.9
23.2
17.2
25.6
24.7
21.6
23.1
20.1
20,2
23.6
25.2
24.0
14.5
18.3
25.7
20.3
20.8
33.0
29.5
19.2
22.3
23.3
20.8
24.1
21.8
25.7
24.8
23.3
23.7
20.8
28.9
22.9
19.8
21.4
25,1
30.6
22,4
24.1
28.4
21.9
23.8
21.5
                                            D-28

-------
         SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE OAWLEY RATS
                    HALE FCX)D CONSUMPTION DATA (9/day)
             ANIMAL  MO.  week  1  week 2  yeek 3  week 4  week 5  week 6 week 7
DOSE  LEVEL
600 mg/kg/day 2980
2981
29S2
29S3
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009 •
17.4
24.3
19.7
22.3
23.3
22,1
18.3
18.8
20.2
19.7
24.7
24.1
na
23.0
21.2
20.6
21.9
20.1
18.9
26.3
12.0
20.8
21.7
22.1
na
20.0
21.7
21.9
.21.1
'21.4
19.1
19.7
24.2
22.4
22.2
22.0
19.3
21.4
23.4
21.3
26.4
26.5
na
na
25.4
24.2
23.0
22.7
24.6
19.7
21.3
23.3
26.4
24.0
na
26.4
23.6
24.3
3.6
22.2
18.1
24.3
24.3
21.4
na
25.6
17.8
21.0
19.7
21.5
25.3
22.2
na
na
22.4
19.0
18.3
na
22.4
18.1
20.2
22.2
24.4
25.1
na
24.1
20.6
21.6
na
20.9
23.8
24.3
26.1
23.6
na
25,6
20.0
23,0
24.0
23.9
26.6
26.8-
na
na
19.1
25.8
22,6
na
24.4
22.1
23.2
20.8
26.2
25.8
na
20.8
19.5
23.3
na
16.8
21.2
Z1.5
20.6
21.8
na
26.4
20.S
22.5
24.4
19,0
26.2
23 .a
na
na
25.1
22.8
21.8
na
23.4
20.2
20.8
21.8
27.4
26.9
na
25.5
21.8
24.3
na
20.1
21.3
19.4
,21.2
23.6
na
23.6
20.7
22.0
23.1
17.6
25.5
24.6
na
na
26.0
na
22.3
na
23.1
19.8
21.0
17.7
28,0
23.0
na
23.2
19.5
21.7
rva
21.0
17.9
18.4
16.3
19.3
na
16.7
15.2
22.8
18.4
19.7
23.2
21.8
na
na
25.6
na
18.7
na
El. 7
18.3
17.9
16.4
22.3
22.4
na
21.0
21.0
21.6
na
18.4
  na  =  no  data  available.
                                        D-29

-------
           SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAQUE DAUIEY RATS
                      HALE FOOD CONSUMPTION DATA Cg/day)
                 ANIMAL NO.  week B  week 9  week  10  week  11  week 12  week 13
    DOSE LEVEL
0 mg/kg/day -' 2881
2882
2883
2884
2885
2886
2SS7
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
na
na
na
na
na
na
na
na
na
na
22.9
16.2
20.2
18.4
20.2
Z0.2
23.5
26.0
22.5
28.9
21.6
25.0
18.9
23.3
20.3
22.3
27.8
22.2
20.7
19.7
na
na
na
na
na
na
na
na
na
na
16.9
24.8
19.4
20.0
20.4
18.3
na
na
na
na
na
08
na
na
na
na
10.8
11.7
14.0
16.6
19.5
10.6
11.8
17.7
17.5
21.8
11.0
16.9
13.3
18.7
19.1
10.7
17.1
17.9
18.2
21.2
na
na
na
na
na
na
na
na
na
na
12.7
16.2
15.1
15.2
19.2
10.5
na
na
na
na
na
na
na
na
na
na
22.5
20.0
21.3
18.3
20.9
20.5
25.0
24.4
22.9
29.0
22.0
25.5
23.3
24.6
21.3
22.8
21.7
12.3
11.2
23.6
na
na
na
na
na
na
na
na
na
na
17.9
20.7
23.6
19.3
19.8
21.8
na
na
na
na
na
na
na
na
na
na
26.1
17.8
21.1
21.4
21.2
23.8
24.8
25.0
22.7
29.4
24.0
26.4
22.5
23,4
21.1
26.2
25.5
24.5
22.1
20.7
na
na
na
na
na
na
na
na
na
na
23.6
22.7
22.9
20.4
22.1
25.8
na
na
na
na
na
na
na
na
na
na
25.9
18.7
21.6
20.3
19.3
23.2
22.5
23.7
21.9
29.3
23.8
26.0
21.3
23.1
21.0
25.3
26.8
24.9
22.0
22.6
na
na
na
na
na
na
na
na
na
na
19.1
26.4
23.1
20.2
21.6
23.!
na
na
na
na
na
na
na
na
na
na
25.4
16.5
20.5
19.5
19.7
21.6
22.7
22.3
18.2
26.2
23.5
25.6
21.6
23.5
19.4
27.6
22.6
24.8
20.7
20.9
na
na
na
na
na
na
na
na
na
na
17.6
24.7
21.2
19.9
7.0
22.2
na = no  data  available.
                                       0-30

-------
         SUBCKRQNJC TOX1CITY OF QRTHO-CRESOL IN SPSAGUE DAWLEY RATS
                   HALE FOCO CONSUMPTION DATA (g/day)
               ANIMAL NO.  week 3  week 9  week 10  week  11  week 12  week 13
  DOSE LEVEL
50 mg/ kg/day . 2930'
(continued} / 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
H954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
16.6
23.1
20.3
22.4
15.3
24.7
24.4
21.6
20.6
15.3
19.2
24.0
24.3
23.5
na
na
na
na
na
na
na
na
na
na
21.4
24.7
18.1
24.1
23.3
20.7
27.0
20.3
23.5
23.3
20.1
22.5
26.0
26.1
21.0
25.0
27.6
10.9
20.9
20.1
12.4
15.9
18.4
21.3
4.0
.a
16.5
16.9
17.7
9.1
12.3
18.4
21.0
24.1
na
na
na
na
na
na
na
na
na
na
20.5
24.6
21.1
25.9
24.6
22.5
28.8
22.4
24.1
24.7
20.5
22.6
24.4
28.3
21.3
25.5
31.3
19.4
35.2
19.7
19.7
22.0
22.0
23.0
19.2
25.2
24.5
21.7
20.3
19.2
21.1
23.4
24,8
23.9
na
na
na
na
na
na
na
ne
na
na
21.9
24.7
20.4
23.0
24.5
22.0
23.5
20.1
24.5
22.4
19.8
22.3
25.4
26.6
20.9
26.1
28.7
21.2
15.7
19.0
19.3
23.3
25.5
25.4
19.9
26.8
24.2
21.7
19.3
20.8
21.9
25.2
26.1
23.9
na
na
na
na
na
na
na
na
na
na
22.2
24.0
21.6
24.6
27.1
21.0
29.5
20.3
23.7
24.6
21.4
21.9
26.9
27.3
22.4
27.5
27.9
20.9
18.5
19.4
18.5
22.7
21.9
23.7
15.4
24.5
9.9
20.9
19.5
19.6
20. B
22.9
25.8
23.7
na
na
na
na
na
na
na
na
na
na
20.5
23.5
21.7
25.1
17.7
21.5
28.8
19.2
23.9
23.8
22.3
22.5
26.8
27.8
22.0
26.7
27.5
20.3
19.3
18.8
16.7
23.0
23.5
24.6
17.4
24.5
24.4
20.0
21.3
16.1
19.3
22.9
25.5
23.8
na
na
na
ra
na
na
na
na
na
na
21.0
19.5
23.7
24.2
25.8
22.6
28.6
20.2
23.9
23.5
20.6
20.8
8.5
26.1
22.0
25.4
25.3
21.5
20.7
16.7
a Value not valid
 na  =  no  data  available.
                                     D-31

-------
       SUBCHRONIC TOX1C1TY OF ORTHO-CRESDL IN SPWGUE DAHLEY RATS
                  HALE FOOD CONSUMPTION DATA Cg/day}
             ANIMAL NO.  yeek 8  week 9  week 10  ye«k 11   week 12 week 13
DOSE LEVEL
600 mg/kg/day 2980
/ 2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3QQ7
3008
3009
na
na
na
na
na
na
na
na
na
na
25.0
22.4
na
na
27,0
na
19.0
na
21.4
16.0
20.1
19.5
25.5
21.2
ni
11.3
na
9.8
na
15.2
na
na
na
na
na
na
na
na
na
na
23.0
22.4
na
na
26.0
na
19.7
na
26.3
16.6
20.7
9.2
23.8
24.6
na
25.7
na
13.9
na
18.1
na
na
na
na
na
na
na
na
na
na
23.1
21.6
na
na
27.9
na
19.8
na
23.2
17.2
4.8
16.4
2B.Q
23.1
na
24.3
na
26.5
na
20,0
na
na
na
na
na
na
na
na
na
na
24.1
22,1
na
na
28.5
na
19.4
na
21.9
18.2
na
22.7
28. Q
23.5
na
21.9
na
28.4
na
20.5
na
na
na
na
na
na
na
na
na
na
23.1
23.6
na
na
28.9
na
21.0
na
22.6
18.7
na
21. a
27.1
24.3
na
24.4
na
28.4
na
20.1
na
na
na
na
na
na
na
na
na
na
21.3
22.1
na
na
27.3
na
19.5
na
22.3
14.7
na
21.8 '
25.8
21.9
na
23.3
na
28.3
na
19.9
na  =  no data  available.
                                  D-32

-------
       SUBCHRQMIC TOXICITY  OF  ORTHO-CRESOL  IN SPRACUE DAWLEY RATS
                     HALE  1=000 CONSUMPTION  DATA  (g)
                            IFeeder  Weights]
                ANIMAL  NO,   new  1   old   1  new  2  old  2  new  3  old  3
 DOSE LEVEL
 0 mg/kg/day
50 ing/kg/day
28S1
2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
292?
292B
2929
452
466
422
435
455
448
447
435
451
432
416
449
447
440
453
462
457
452
464
459
450
432
46a
426
450
415
439
432
441
418
422
388
445
428
435
458
428
424
457
443
448
453
438
449
457
438
290.2
307.4
267.1
247.2
276,2
264.5
288.2
291.9
294.5
272.2
244.6
299.4
283.3
290.4
283.2
301.4
298.4
264,3
316.9
261.9
274.6
253.2
318.6
251.5
292.5
242.1
251.6
264.4
280.6
253.5
246.7
212.8
288.7
246.9
280.9
296.8
265.9
262.0
298.8
249.9
283.0
303.6
288.9
294.6
297.5
264.9
600.6
543.8
551.3
579.6
561.5
600.4
579.6
559.2
574.9
614.4
576.2
565.4
620.0
605.1
565.0
560,6
588.1
577.0
5S8.5
578.2
619.4
594.9
598.6
608.9
627.3
577.8
556.1
579.9
568.8
579.7
538.3
585.9
613.0
554.3
587.5
579.4
594.1
599.4
620.2
621.0
590.2
582.3
575.1
590.2
590.3
571.4
364.1
419.8
378.6
369.8
364.4
406.3
396.5
399.3
388.0
452.6
391.8
405.1
439.0
432.0
373.5
374.0
403.2
463.6
424.2
341.5
419.4
404.1
426.1
421.1
450.0
378.0
343.4
395.8
383.8
474.8
357.7
400.0
430.2
347.8
419.6
396.4
398.0
413.7
432.4
398.6
395.1
386.9
402.6
415.2
405.0
381.0
541.3
504.9
502.1
531.1
529.4
544.0
545.8
513.6
526.6
538.5
505.1
501.3
542.8
463.1
484.1
476.5
521.3
521.4
466.9
453.6
527.8
495.7
513.0
522.1
518.1
450.1
486.2
474.8
466.2
505.8
478.8
505.6
471.7
502.7
497.0
491.5
477.2
487.8
463.3
454.5
448,8
467.1
483.2
494.9
472.8
505.1
385.7
344.9
331.6
333.8
349.9
346.1
369.0
373.4
353.2
380.7
330.7
357.5
371.3
315,9
317.7
302.5
345.2
286.5
299.9
215.9
349.9
305.8
355.2
322.2
343.1
258.9
269.2
309.7
337.5
348.7
381.0
346.9
315.9'
324.2
321.7
309.5
305.3
303.6
296.9
239.3
279.5
281.0
329.0
344.4
295.9
318. 1
                                             D-33

-------
      SUBCHRONIC TOXICITY OF ORTHO-CRESOL  IK  SPRAGUE DAUIEY RATS
                    KALi FOOD CONSUMPTION  DATA  (g)
                           [Feeder Weights]
               ANIMAL NO.   new  1   old  1   new  2  old  2  new  3  old  3
DOSE LEVEL--
50 mg/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
449
464
423
412
432
451
415
447
453
481
472
427
416
442
529
459
412
443
439
430
446
443
430
412
452
419
428
406
438
429
395
427
422
407
417
476
423
423
432
451
408
475
422
416
290.6
313.6
272.0
247.2
286.0
274.6
244.4
284.4
231.6
319.3
312.3
248.7
233.7
272.4
400.3
308.2
219.7
286.8
281.4
237.1
290.0
263.5
268.8
258.9
308.5
250.1
280.0
260.7
315.0
269.3
199.8
293.2
26S.O
250.6
250.3
326.6
250.9
240.3
285.3
285.4
234.5
335.6
250.8
302.8
603.1
569.8
590.5
602.4
578.3
596.0
624.0
620.6
607.2
712.0
582.7
600.6
566.5
619.9
737.6
569.1
608.1
603.0
615.4
579.3
592.1
590.8
570.4
594.2
658.8
581.2
597.2
577.0
178.9
571.3
607.8
566.8
537.4
551.4
576.8
605.3
581.3
569.0
570.2
609.7
607.3
608.5
593.1
591.7
403,1
430.5
383,3
413.8
406.2
381.5
415.9'
430.6
425.3
535.3
395.8
402.1
352.3
414.5
583.3
386-3
420.3
422.8
445.4
363.1
413.7
412.6
398.1
422.9
490.4
388.3
331.7
419.0
433.3
395.8
414.2
379.0
366.0
383.5
399.8
432.9
393.4
387.1
406.1
407.8
416.8
438.7
419.3
428.5
465.8
477.1
462.9
470.8
483.6
477.0
505.4
486.8
470.4
535.3
504.6
496.6
477,7
502.2
583.3
488.0
483.8
4S2.2
505.5
485.2
485.0
514.2
510,6
518.0
558.5
479.5
484.9
482.9
510.2
512.7
507.7
460.0
488.4
469.4
481.3
510.0
473.7
490.9
504.0
472.3
502.6
438.7
518.3
533.6
305.3
304.6
231.8
290.0
325.9
284.6
322.3
310.6
293.0
377,1
347.4
305.3
273,0
316.0
439.3
325.4
303.0
309.5
362.1
286.1
310.8
348.8
356.6
364.3
394.8
279.7
346.2
316.1
364.2
354.7
312.5
301.0
310.9
305.6
323.9
345.8
311.4
308.9
376.6
310.5
315.7
285.9
365.4
395.7
                                       D-34

-------
       SU8CHRGNIC TOXICtTY OF Q8THQ-CRESQL  IN SPRAGUE DAWLSY RATS
                   HALE FOOD CONSUMPTION  DATA 
-------
       SUBCHRQN1C TOXICITY  OF  ORTKO-CRESOL  IN SPRAGUE DAWLEY RATS
                     HALE  FOOD CONSUMPTION  DATA 
-------
      SUBCHROMIC TOXICITY OF  ORTHQ-CRESOL  IN SPRAGUE DAyLEV RATS
                    HALE FOOD CONSUMPTION  DATA  (g)
                           [Feeder Weights]
               ANiHAL NO.   new  4   old   4   new  5  old  5  new  6  old  6
DOSE LEVEL
50 mg/ kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
461.
1
454.6
433.
452.
439.
435.
414.
439.
413.
544.
438.
438.
439.
417,
475.
410.
407.
409.
8
0
7
4
5
4
9
5
8
6
9
8
2
4
6
2
452.4
436.
483.
464.
458.
463.
465.
457.
448.
411.
456.
421.
469.
433.
423.
482.
454.
435.
440.
422.
420.
437.
440.
453.
462.
432,
6
7
5
3
2
2
1
3
8
8
8
5
3
4
6
5
9
2
2
\
2
4
7
3
1
316.
282.
256.
Z69.
288.
244.
232.
266.
221.
398.
284.
241.
233.
231.
325.
238.
212.
226.
291.
233.
275,
267.
272.
259.
279.
259.
292.
217.
286.
253.
257.
270.
233.
307.
290.
261.
245.
214.
263.
246.
231.
274.
253.
254.
2
8
5
7
9
8
8
1
7
2
7
8
0
2
0
8
9
8
8
3
3
1
0
9
5
5
7
2
7
1
4
0
3
6
a
0
6
4
8
8
8
2
6
8
461
451
438
4S4
492
446
473
438
477
550
491
460
463
511
592
501
457
486
505
518
499
492
492
478
563
500
531
431
480
500
483
476
491
516
526
496
506
473
518
537
499
516
526
480
.5
.1
.2
.6
.1
.8
.7
.3
.3
.3
.2
.9
.0
.1
.7
.8
.7
.3
.8
.1
.0
.2
.2
.1
.5
.2
.0
.5
.6
.7
.0
.4
.5
.9
.6
.9
.7
.7
.1
.1
.9
.6
.0
.8
314.
274.
266.
311.
328.
267.
299.
287.
300.
399.
330.
234.
264.
332.
434.
334.
256.
318.
360.
320.
299.
327.
317.
282.
407.
313.
378.
245.
311.
335.
275.
322.
316.
347.
363.
335.
329.
261.
357,
354.
295.
367.
406.
323.
6
3
6
1
1
7
1
8
9
9
5
4
2
9
6
7
2
2
0
1
7
1
9
3
7
2
9
6
7
8
5
2
5
5
4
4
9
0
7
6
4
7
6
5
498
507
496
495
507
505
505
480
496
488
486
492
470
525
519
505
476
498
498
489
506
469
470
494
520
482
474
474
508
478
482
484
471
508
516
499
479
479
499
473
471
489
483
465
.8
.9
.1
.6
.5
.5
.7
.0
.6"
.7
.6
.7
.9
.8
.9
.5
.6
.8
.6
.5
.0
.9
.0
.4
.6
.8
.0
.3
.0
.4
.2
.8
.5
.9
.7
.5
.7
.8
.4
.3
.5
.7
.3
.6
350.9
321.4
327.9
312.9
348.9
299.4
316.5
320.7
328.6
354.0
315.6
323.5
267.0
342.8
367.3
330.3
269.1
307.4
335.1
299.5
304.1
290.4
287.3
280.8
365.9
291.5
310.6
293.7
337.9
306.7
297.0
321.5
279.7
339.3
335.7
328.7
2S4.6
266.3
328.2
280.2
244.3
341.8
321.8
325.2
                                          D-37

-------
      SUBCHRQNIC  TOXICITY OF ORTHO-CRESOL  IH SPRAGUE DAWLEY RATS
                  MALE  FOOD CONSUMPTION  DATA (g)
                         [Feeder Weights]
              ANIMAL NO,  new  4  old  4 new  5  old  5  new  6  old  6
DOSE LEVEL.
600 mg/icg/day 2980
Z981
2932
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
479.1
463.6
447.6
430.8
na
401.9
440.2
461.8
452.8
451.5
415.2
503.8
na
na
461.0
457.6
432.4
na
447.7
420.9
435.4
413.7
441.0
430.4
na
432.8
455.7
429.1
na
430.8
312.3
293.2
264.7
265.7
na
222.9
299.9
300.5
285.0
284.5
229.3
315.9
na
na
327.5
276.8
274.2
na
277.0
266.5
272.8
267.9
257.3
250.1
na
287.1
319.2
266.3
na
313.3
535.1
501.0
483.2
467.2
na
500.7
521.6
503.3
470.4
498.7
484.6
470.7
na
na
489.2
479.8
497.2
na
497.2
478.0
481.2
500.4
481.6
483.3
na
474.2
496.8
442.6
na
452.4
386.7
350.6
344.3
314.4
na
315.6
378.3
345.7
299.7
365.6
300.9
304.3
na
na
313.7
319.9
344.9
na
333.7
336.5
335.5
347.6
289.5
294.9
na
295.5
344.4
272.4
na
311.8
481.6
499.8
472.5
471.0
na
464.9
495.7
501.7
461.0
507.1
445.4
484.0
na
na
437.2
na
493.6
na
488.0
489.0
479.4
486.4
451.2
464.7
na
489.1
478.5
486.0
na
475.6
332.2
364.3
324.1
306,1
na
299.8
350.9
347.4
299.5
384.2
266.7
311.8
na
na
305.5
na
337.2
na
326.1
350.2
332.5
362.8
255.4
303.4
na
326.4
342.0
334.0
na
328.3
na = no  data  available.
                                     D-38

-------
           SUBCHRONIC TOXICm OF ORTHO-CRESOL  IN SPRACUE PAWIEY RATS
                       MALE FOOD CONSUMPTION  DATA (g)
                              [Feeder Ueightsl
                   ANIMAL NO.  new  7  old  7  new  8  old  8  new  9  old  9
     DOSE LEVEL
0 mg/kg/day 2831
2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
416
344
361
344
379
326
357
325
331
331
491
498
494
476
480
483
474
490
493
493
473
491
494
475
478
485
475
490
465
490
349
411
358
356
377
348
336
348
329
320
486
475
472
496
474
477
.2
.6
.9
.5
.6
,8
.6
.1
.8
.9
.4
.8
.3
.9
.7
.7
.7
.7
,1
.5
.7
.8
.3
.4
.0
.3
.9
.1
.7
.4
.8
.5
.3
.3
.6
.2
.9
.5
.5
,5
.5
.7
.9
,9
.1
.9
300
300
324
283
313
290
267
298
297
281
319
379
,1
,3
.9
.7
.7
.8
.1
.4
.9
.4
.8
.1
346.5
340
327
336
320
315
322
305
321
313
342
298
318
321
274
335
312
329
330
359
347
348
367
296
297
283
297
267
346
312
318
355
330
292
.1
.0
.0
.8
.5
.9
.0
.2
.2
.8
.6
.7
.4
.5
.5
.6
.0
.0
,1
.9
.5
.2
.3
.1
.8
.5
.8
.0
,9
.0
.3
.6
.1










421
na
na
na
na
na
na
na
na
na
na
.7
.426.6
425
415
420
.7
.4
.0
427.3
413
425
435
423
427
426
474
437
423
421
421
419
422
419










428
426
438
430
431
441
.4
.0
.0
.7
.1
.6
.3
.2
.4
.5
.1
.0
.6
.4
na
na
na
na
na
na
na
na
na
na
.0
,9
.8
.0
.9
.3
na
na
na
na
na
na
na
na
na
na
261.2
313.3
284.2
286.9
278.5
286.2
249.1
242.9
277.4
221.5
275.6
251.5
342.3
274.0
281.6
265.3
226.2
263.3
277.4
281.7
na
na
na
na
na
na
na
na
na
na
309.9
253.1
302.9
289.9
289.0
313.5










418
429
419
443
381
434
391
424
431
446
433
443
472
454
438
445
422
423
418
421










398
380
404
432
436
437
na
na
na
na
na
na
na
na
na
na
.3
.3
.3
.6
.9
.1
.5
.2
.8
.6
.7
.4
.5
.1
.8
.1
.5
.9
.9
.8
na
na
na
na
na
na
na
na
na
na
.4
.0
.2
.6
,9
.9










342
na
na
na
na
na
na
na
na
na
na
.8
347.4
321
.3
327.2
245
359
308
300
309
293
356
325
379
322
304
370
302
298
291
273










309
266
298
326
302
364
.6
.9
.8
.2
.1
.7
.9
.3
.2
.9
.8
,2
.7
.5
.2
.4
na
na
na
na
na
na
na
na
na
na
.6
,9
.6
.2
.6
.7
na = no  data  available.
                                            D-39

-------
     SUBCHROMIC TOXICITY OF QRTHQ-CRESOL IN SPRAGUE DAUIEY RATS
                  HALE FOOD CONSUMPTION CATA (3)
                        [Feeder Weights]
             ANIMAL  NO.  new 7  old 7  new 8  old 8  new 9  old  9
DOSE  LEVEL
50 rag/ kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
484.2
487.4
489.0
456.4
472.5
452.0
478,5
465.3
485.4
430. 2
486.6
452.9
452.0
447,9
367.3
351.4
421.4
381.9
358.9
395.0
349.9
338.8
509.1
345.3
523.6
451.1
469.9
468.8
487.1
485.8
456.6
436.3
470.8
468.0
468.0
481.9
492.9
544.7
465.9
474.5
453.8
493.4
475.3
483.4
359.6
319.9
335.9
294.3
351.9
272.7
305.9
314.0
323.8
339.2
345.2
288.0
275.3
279.6
338.4
296.4
344.3
320.9
296.6
329.0
290.9
300.5
464.5
298.6
377.8
282.3
317.2
289.1
313.5
322.9
290.6
340.9
268.2
307.4
329.1
331.8
317.2
330.3
308.9
306.1
255.3
339.8
308.9
333.0
437.9
433.3
423.1
426.4
424.4
416.4
416.9
425.4
421.5
432.3
424.5
425.4
427.2
429.4
na
na
na
na
na
na
na
na
na
na
443.9
423.7
415.9
421.9
415.4
425.9
424.5
422.7
425.3
418.8
419.6
421.1
429.4
445.0
428.2
426.9
425.9
438.9
417.4
415.5 .
321.8
276.7
277.2
269.3
317.3
243.7
246.3
274.5
277.3
325.0
2S9.9
257.6
253.6
264.8
na
na
na
na
na
na
na
na
na
na
294.0
250.5
289.2
253.1
252.1
2B1.2
235.7
280.7
260.9
255.8
278.6
263.5
247.2
262.4
281.2
252.2
232.4
362.8
271.4
274.5
426.1
440.8
437.3
430.9
451.7
382.6
418.4
449.7
505.3
506.7
458.5
460.9
497.5
431.5
na
na
na
na
na
na
na
na
na
na
426.2
419.1
457.3
437.3
442.5
439.2
415.9
425.7
435.5
411.9
450.2
436.8
434.5
428.5
431.0
478.7
463.0
438.4
493.6
433.9
339.5
329.2
308.4
281.8
423.6
475.7
302.6
331.5
381,4
443.2
372.2
332.1
350.6
262.5
na
na
na
na
na
na
na
na
na
na
282.7
246.7
309.5
255.8
270.5
282.0
214.1
268.9
266.8
238.7
306.9
278.7
263.5
230.7
281.8
300.3
243.8
302.8
247.2
296.3
 na  =  no data  available.
                                      D-40

-------
       SUBCHRONIC TOX1C1TY OF ORTHO-CRESOL IN SPRAGUS DAULEY RATS
                    MALE FOOD CONSUMPTION DATA (g)
                          [Feeder Weights]
               ANIMAL  NO.  new 7  old  7  new 8  old 8  new  9  old  9
  DOSE LEVEL,
600 mg/k9/day 2980
2981
2982
2983
2984
29S5
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
449.2
502.4
357.7
363.4
na
355.0
350.9
347.4
350.9
334.2
475.8
466.3
na
na
449.6
na
494.1
na
475.5
466.9
454.9
470.8
445.5
442.4
na
455.7
456.1
435.5
na
470.8
395.4
447,2
325.2
305.5
na
321.6
305.3
301.8
295.7
344.8
313.1
313.6
na
na
Z70.6
na
363.3
na
323.7
338.9
329.6
355.9
289.7
285.5
na
308. 6
393.2
254.6
na
341.9
na
na
na
na
na
na
na
na
na
na
426.6
431.5
na
na
422.9
na
424.5
na
422.4
430.2
421.2
422.1
418.9
420.6
na
426.9
na
423.6
na
417.4
na
na
na
na
na
na
na
na
na
na
251.6
274.9
na
na
234,2
na
291.5
na
272.3
318.5
280.8
285.3
240.7
272.3
na
348.0
na
355.2
na
310.9
na
na
na
na
na
na
na
na
na
na
485.8
490.9
na
na
432.6
na
446.1
na
438.9
433.5
492.6
465.1
463.8
458.8
na
434.3
na
453.8
na
445.2
na
na
na
na
na
na
na
na
na
na
325.1
333.9
na
na
250.7
na
308.1
na
254,6
317.5
347.5
401.0
297.0
286.3
na
254.2
na
356.4
na
318.3
na = no  data  available.
                                        D-41

-------
                    SU3CHRONIC  TOXIC!TY OF OSTHO-CRESOL IN SPRAGUE DAUtEY RATS
                                HALE FOOD CONSUMPTION DATA (g)
                                       [Fesdsr Weights]
                 ANiMAL NO.  new  10  old  10  new  11  old  11  ney  12  old  12  new  13  old  13
   DOSE LEVEL
0 mg/kg/day 2881
2882
2883
2884
2885
2886
2887
28S8
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
na
Hi
na
na
na
na
na
na
na
na
425.0
423.2
425,4
424.8
405.4
424.3
423.7
423.8
418.3
422.9
421.5
424.0
472.0
420.0
426.9
424,1
402.4
420.5
428.0
424.6
na
na
na
na
na
na
na
na
na
na
433.2
431.4
437.5
425.3
430.6
432.6
na
na
na
na
na
na
na
na
na
na
267.3
282.9
2?6.0
297.0
259.2
280.5
248.7
252.8
257.7
219.8
267.5
245.5
308.6
247.6
278.1
264.3
250.5
334.3
349.8
259.6
na
na
na
na
na
na
na
na
na
na
307.9
286.8
272.6
290.4
291.8
280.2
na
na
na
na
na
na
na
na
na
na
425.7
425.9
426.5
429.8
427.0
426.2
427.2
427.2
428.2
430.7
429.2
431.4
429.7
426.3
426.4
429.3
426.9
429.2
429.1
427.5
na
na
na
na
. na
na
na
na
na
na
434.3
438.0
432.3
436.2
434.1
442.2
na
na
na
na
na
na
na
na
na
na
243.3
301.6
278.6
280.1
278.5
259,3
253.8
252.3
269.0
225.2
261.0
246.9
272.3
262.4
278.6
246.1
248.7
257.4
274.2
282.4
na
na
na
na
na
na
na
na
na
na
269.1
278.8
272.3
293.5
279.5
261.6
na
na
na
na
na
na
na
na
na
na
455.4
465.5
455.4
455.3
466.2
459.3
464.6
458.3
464.4
448.2
466.0
458.1
457.7
484.6
456.1
454.1
453.4
453.2
450.4
438.8
na
na
na
na
na
na
na
na
na
na
436,6
449.7
452.1
451.5
445.6
442.0
na
na
na
na.
na
na
na
na
na
na
273.8
334.5
304.0
313,0
331.3
297.1
307.3
292.7
311.3
243.4
299.5
276.3
308.7
323.1
309.1
276.7
266.1
278.9
296.7
280.8
na
na
na
na
na
na
na
na
na
na
303.0
264.6
290.5
309,8
294.6
280.1
na
na
na
na
na
na
na
na
na
na
463.8
466.8
429.8
443.9
470.1
463.1
465.2
447.2
436.3
457.7
470.7
466.7
458.1
468.3
480.1
485.3
443.7
443.5
461.3
426.5
na
na
na
na
na
na
na
na
na
na
447.5
489.2
451.4
457.6
444.3
423.9
na
na
na
na
na
na
na
na
na
na
311.6
36S.1
307.0
307.1
332.3
333.3
329.1
291.0
308.6
300.3
306.4
313.2
307.0
327.1
344.4
319.6
285.7
270,2
316.4
280.5
na
• na
na
na
na
na
na
na
na
na
324.2
316.6
302.7
318.3
395.0
290.9
na = no  data available.
                                               D-42

-------
                     SUBCKRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAVJLEY RATS
                                  HALE FOOD CONSUMPTION DATA 
-------
                 SUBCHRONIC  TOXIC!TY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                             MALE FOOD CONSUMPTION DATA (g)
                                    [Feeder Weights]
              ANIMAL NO.  new  10  old  10  new  11  old  11  new  12  old  12  new  13  old  13
DOSE LEVEL
600 mg/kg/day 2980
2981
29S2
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
na
na
na
na
na
na
na
na
na
na
420.0
422,9
na
na
424.1
na
420.6
na
444.6
423.6
434.7
423.0
436.0
445.1
na
422.5
na
431.0
na
427.2
na
na
na
na
na
na
na
na
na
na
258.4
271.4
na
na
228.6
na
282.1
na
282.4
302.9
401.2
307.9
239.7
283.6
na
252.2
na
245,8
na
287.0
na
na
na
na
na
na
na
na
na
na
438,4
426.7
na
na
430.5
na
427,2
na
437.6
430.6
na
426.3
424.3
439.3
na
425.7
na
434.8
na
429.4
na
na
na
na
na
na
na
na
na
na
269,9
271,7
na
na
231.0
na
291.3
na
234,2
303.4
na
267.5
228.2
274.8
na
272.1
na
235.9
na
285.6
na
na
na
na
na
na
na
na
na
na
455.1
449.2
na
na
442.7
na
442.9
na
445.1
468.7
na
441.9
444.4
467.6
na
478.2
na
432.2
na
462.5
na
na
na
na
na
na
na
na
na
na
293.4
283.7
na
na
240.4
na
296.2
na
286.7
337.7
na
289.3
254.7
297.2
na
307.1
na
233.4
na
322.1
na
na
na
na
na
na
na
na
na
na
518.3
554.6
na
na
506,2
na
533.2
na
500.7
517.8
na
463.7
517.3
536.1
na
518.5
na
502. 9
na
505.0
na
na
na
na
na
na
na
na
na
na
390.5
422.1
na
na
315.3
na
416.0
na
366.8
414.8
na
311.2
337.0
404.6
na
355.7
na
304.8
na
366.0
na =  no  data available.
                                                  D-44

-------
           SUBCHRQN1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE  OAWLEY  RATS
                      FEMALE FOOD CONSUMPTION DATA (g/day)
                ANIMAL NO.  week 1  week 2  week 3  week 4  week  5  week 6  week 7
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
3013
30 H
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
30Z8
3029
3030
3031
' 3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
14.8
17.2
14.6
17.0
18.5
16.1
15.8
15.5
18.4
13.5
14.5
13.8
ia.3
16.1
18.0
15.0
15.1
15.6
14.3
16.8
13.9
13.4
13.3
14.3
17.4
13.2
15.5
13.9
14.8
16.6
15.1
13.3
14.9
16.0
15.8
14.3
14.7
12.8
12.7
16.1
0.7
17.2
15.7
15,1
14.8
13.3
17.2
16.1
14.3
23.5
20.8
13.6
17,7
18.6
18.6
15.8
18.5
2.5
21.6
12.0
35.5
19.8
16.9
17.0
8.7
.24.7
16.8
12.2
17.9
13.9
14.2
23.1
14.9
11.1
0.6
31.0
16.1
14.4
16.0
17.6
17.7
16.1
22.4
7.8
14.8
18. 2
16.8
18.0
19.4
16.2
15.5
16.6
26.3
15.6
14.1
18.9
23.3
17.2
16.8
16.4
13.9
14.4
17.2
14.8
44.1
15.0
10.2
24.1
16.3
15.6
15.0
17.2
15,4
19.8
13.9
22.6
17.3
14.5
13.2
18.5
27.4
14.3
14.8
14.1
16.3
14.8
17.1
14.2
9.4
20.1
12.6
17.1
14.3
16.4
18.8
15.3
15.2
15.7
1,7.9
16.6
13.5
23.7
22.3
16.3
16.2
15.9
15.8
16.0
15.6
13.9
24.3
16.5
18.7
16.6
16.7
14.8
15.0
18.0
15.5
14.9
14.9
14.9
19.4
15.8
15.7
17.8
14.0
14.8
14.5
14.4
15.3
15.7
15.8
15.0
16.6
14.0
13.3
26.0
13.8
15,4
18.7
14.5
14.4
15.3
17.1 '
20.1
14,8
'18.4
19.9
16.4
16.8
16.0
15.4
13.3
16.7
13.9
28.5
13.7
19.4
15.4
17.0
14,0
14.8
18.0
13.6
15.5
14.3
14.3
17.8
16.1
17.9
16.6
14.7
13.9
14.0
14.7
17.1
30.2
15.8
14.9
15.1
13.6
13.8
16.4
14.1
17.2
17.2
15.4
14.4
16.9
15.5
15.6
14.9
20.5
21.7
15.0
15.3
17.1
14.6
13.9
15.6
14.8
27.0
28.2
19.2
16.3
17.9
13.8,
16.0
17.6
15.1
15,1
14.5
13.3
17.0
16.4
16.4
17.6
15.3
14.7
13.8
14.7
17.0
13.8
15.9
11.9
15.6
13.7
15.3
20.1
15.3
16.4
18.1
16.0
15.8
15.7
13.4
11.9
10. 1
15.7
13.0
16.5
14.4
14.2
13.7
9.3
13.9
13.1
22,1
13.3
17.5
13.4
12.9
12.2
13,1
14.7
14.5
13,4
13.3
12.0
16.3
13.2
15.1
13.7
13.1
13.0
27.3
1.7
14.1
32.1
.a
23.9
7.0
3.8
5,3
15.5
13.5
15.9
13.7
14.4
14.0
13.8
                   aValue not valid
                                                    D-45

-------
          SUBCHRON-IC TOXICITY OF ORTHO-CRESOl IN SPRAGUE DAWLElf RATS
                     FEMALE FOOD CONSUMPTION DATA (S/day)
               ANIMAL NO.  yeek 1  week 2  week 3  week 4  week 5  week 6  week 7
DOSE LEVEL
50 i^/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
13.9
14.7
14.5
18.0
15.7
15.8
11,7
13.9
13.7
17.9
15.5
14.0
16.2
15.6
15.4
15.4
15.6
13.9
14.6
15.3
14.7
17.1
13.7
16.4
17.4
13.8
17.3
15.9
16.2
14.8
15.0
17.0
14.0
14.9
14.4
18.6
13.3
17.1
21,4
17.4
16.8
16.1
16.2
19.6
17.7
11.5
21.9
14.8
24,9
18.7
14.6
16,5
12.7
22.1
18.0
16.3
23.2
12,7
17.9
17.9
21.9
14.1
15.3
15.3
14.5
13.0
14.8
6.3
11.2
Z3.4
11.8
18.2
21.2
6.3
16.6
17.3
14.3
15.6
15.3
18.0
15.3
16.4
16.9 •
10.1
18.3
16.5
15.0
17.8
21.1
16.4
17.6
17.8
19,1
18.1
14.9
16,6
15.7
20.3
16.4
15.4
17.2
16.9
12.7
19.6
22.7
14.4
14.5
12.3
12.5
12.6
13.0
26.3
18.4
4.8
21.4
16.1
14.9
25.4
5,6
19.7
13.8
13.1
14.6
16.4
14,1
15.7
13.4
32.4
15.4
5.2
22.8
15.2
14.7
15.7
15.1
19.4
14.7
20.8
13.8
16.8
26.0
18.0
15.4
15.9
18.8
17.4
18.9
17,0
22.2
15.2
16.6
15.5
13.6
13.0
13.5
15.3
18.0
12.2
15.8
15.4
19.5
15.6
15.7
14.4
14,3
14.3
14.5
18.7
15.4
17.8
14.3
30.2
17,4
16.0
9.4
16.5
17.1
15.7 "
15.9
19.6
15.8
17.8
12.6
16.8
16.4
17.1
15.1
13.9
18.3
17.4
16.2
15.4
20.9
13.5
17.3
15,5
13.5
12.7
12.8
15.3
16.5
12.8
16.4
17.4
21.3
15.7
15.7
15.0
14.5
15,0
16.2
17.5
14.7
15.7
13.1
25.3
16.0
14.4
15.6
17.9
16.4
16.5
16.3
20.2
16.2
17.2
13.2
17.8
17,6
18.5
16.0
14.3
20.3
18.7
14.3
15.2
18.7
14.8
16.7
17.1
14.7
15.1
14.2
14.4
17,3
13.1
16.7
18.2
15.5
16.1
14.9
14.2
14.7
15.2
15.7
18,3
14.2
16.8
14,3
23.0
17.7
9.7
14.2
18.3
15.3
14.7
15-7
17.4
15.2
17.4
12.5
16.3
15.8
14.0
14.7
12.9
15.8
16.5
15.7
11.0
19.6
11.0
11.0
13.6
.a
14.2
22.6
14.1
12.3
11.9
13.9
15.4
13.6
12.8
14.8
12.3
12.8
13.6
13.2
16.1
11.9
14.5
13.5
13.9
13.7
11.9
11.0
15.5
                         not valid
                                              0-46

-------
       SUBCHRONIC TOXICITY OF CRTHO-CRESOL IN SPRAGUE DAWLEY RATS
                FEMALE  FOOD CONSUMPTION DATA Cg/day)
           ANIMAL NO.  week 1  week 2 week 3 week 4  week 5  week 6  week 7
DOSE LEVEL
600 ms/ kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
11.9
12,6
15.3
15.5
14.2
15.8
12.8
14.3
13.9
rva
13.9
12.3
13.4
11.4
13.7
na
15.0
15.9
9.7
13.4
12.6
12.2
11.5
13.2
15.5
14.9
12.5
14.8
12.0
19.8
14.7
13.8
15.5
16.9
15.1
16.7
13.0
18. 1
15.5
na
15.6
13.3
14.1
13.1
15.0
na
14.0
17.7
14.1
14.2
14.2
14.7
9.9
13.5
18.0
7.2
0.2
16.5
13.4
18.6
na
10.6
13.5
14,1
13.8
15.3
12.4
13.0
11.5
na
na
na
13.4
32.8
13.5
na
13.3
15.0
12.2
na
na
na
na
12.7
15.4
na
na
14.5
na
17.2
na
13.7
15.4
16.3 •
U.2
17.4
13.6
14,6
14.3
na
na
na
15.2
13.8
17.2
na
13.3
23.4
14.0
na
na
na
na
13.0
16.8
na
na
17.2
na
19.8
na
13.4
14.1
16.1
14.5
12.6
12.8
13.8
12.8
na
na
na
14.0
13.6
na
na
14.4
19.3
15.0
na
na
na
na
15.5
16.9
na
na
16.9
na
20.3
na
na
15.5
13.3
15,1
20,1
12.4
14.1
15.6
na
na
na
na
na
na
na
15.4
32.3
14.0
na
na
na
na
13.5
13.6
na
na
16.6
na
na
na
'na
11.1
14.2
12,3
9.9
8.1
10.7
10,0
na
na
na
na
na
na
na
12.0
15.6
12.1
na
na
na
na
12.3
12.1
na
na
14.8
na
na
na •= no  data available.
                                      D-47

-------
          SUBCHRON1C TOXICiTY OF ORTHO-CRiSOL IN SPRAGUE DAWLEY RATS


                    FEMALE FOOD CONSUMPTION DATA 
-------
        SUBCHRONIC TOXICITY OF ORTHO-CRESDL IN SPRAGUE DAULEY  RATS
                  FEMALE FOOD CONSUMPTION DATA (g/day)
              ANIMAL NO.  week 8  week 9  week 10  yeek 11  week 12  week 13
 DOSE LEVEL
50 rng/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
.3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
14,1
13.0
13.4
18.0
13.8
16. 6
12.2
16.6
19.9
15.3
4.0
14.0
13.7
14.8
na
na
na
na
na
na
na
na
na
na
13.8
12.0
13.8
16.2
13.8
14.4
13.4
12.5
12.3
12.9
14.5
17.0
12.3
15.6
12.0
15.5
15.8
14.6
12.4
16.6
14.8
14.7
14.4
19.2
14.4
. 17.0
12.3
17.2
18.4
17.8
14.8
14.4
16.2
16.7
na
na
na
na
na
na
na
na
na
na
15.1
12.6
16.2
15.9
16.4
13.1
20.0
13.5
13.0
18.3
15.0
1.5
13.5
14.8
8.8
18.1
15.6
15.0
12.8
16.2
15.6
14.7
14.9
17.7
14.9
18.4
12.9
18.1
16.2
16.5
15.1
14.5
16.9
17.5
na
na
na
na
na
na
na
na
na
na
14.9
9.9
13.0
15.1
28.0
14.3
13.3
13.8
10.3
12.7
14.0
15.3
12.0
14.3
13.6
18.9
14,8
14.2
13.4
14.7
15.4
14.4
14.0
17.6
13.3
15.9
12.9
17.5
15.1
16.1
15.0
11.4
17.0
18.0
na
na
na
na
na
na
na
na
na
na
13.1
9.9
13.7
16.5
16.2
14.3
23.0
12.6
10.8
13.8
13.4
16.7
12.4
14.3
13.9
17.9
13.3
13.4
12.5
13.3
14.1
13.2
14.9
17.1
14.3
16.4
12.1
15.2
15.7
16.8
14.2
10.8
16.2
17.2
na
na
na
na
na
na
na
na
na
na
13.5
10.8
14.3
12.9
15.9
15.4
13.2
9.4
16.1
12.6
16.7
11.2
13.0
14.3
12.9
18.2
14.4
13.8
13.3
14.8
14.7
12.3
14,3
17. a
14.2
17.7
12.3
15.9
16.0
17.8
14.9
14.0
18.5
15.9
na
na
na
na
na
na
na
na
na
na
13.4
11.5
14.5
16.9
17.4
13.5
13.1
13.9
13.3
13.2
15.6
13.6
12.8
15.1
11.5
15.5
14.3
13.9
13.0
14.4
na = no  data  available.
                                         D-49

-------
       SUBCHRQN1C TQXICITT OF QRTHQ-CRESQL  IN SPRAGUE DAWLEY RATS
                 FEMALE FOOO CONSUMPTION DATA (g/day)
             AH1MAL NO.   week 8  week 9  week 10 week 11  week 12  week 13
DOSE LEVEL
600 sig/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
312?
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
12.6
18.5
13.0
na
na
na
na
11.7
12.4
na
na
16.0
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
12.5
16.3
13.5
na
na
na
na
12.7
15.8
na
na
14.6
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na'
na
na
13.8
16.3
12.5
na
na
na
na
12.4
16.9
na
na
14.9
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
14.4
15.5
12.6
na
na
na
na
12.8
17.5
na
na
15.1
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
14.5
16.8
12.8
na
na
na
na
13.8
14.1
na
na
15.2
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
10.7
15.3
11.7
na
na
na
na
11.5
14,6
na
na
14.8
na
na
na = no  data  available.
                                      D-50

-------
       SUBCHRONIC TOXIC1TY  OF  ORTHO-CRESOL  IN SPRAGUE DAULEY RATS
                    FEMALE  FOCO  CONSUMPTION DATA (g)
                            [Feeder Ueights]
                ANIMAL HO.   new   1  old   1  neu  2  old  2  new  3  old  3
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3D41
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
457
465
501
462
487
428
450
453
432
467
423
437
418
413
395
340
345
400
388
40S
394
375
392
367
433
372
370
356
340
437
408
370
399
404
384
414
374
386
388
395
385
392
418
419
358
404
353.5
344.9
399.1
342.8
357.7
315.6
339.2
344.4
303.5
372.4
321.2
340,6
289.9
300.6
269.1
235.1
239.1
290.8
283.0
290.5
296.9
281.2
299.1
266.7
311.1
279.6
261.3
258.7
236.4
320.7
302.6
277.1
294.8
291.9
273.4
313.9
270.8
296.3
299.0
282.3
380.1
271.9
307.9
313.2
254.7
310.7
704.1
684.0
673.0
718.5
694.4
695.3
712.1
689.4
682.8
715.4
587.6
587.1
739.4
634.5
666.5
704.5
571.3
590.0
597.4
663.9
580.6
578,5
598.1
589.2
739.4
598.8
588.8
588.7
612.2
723.2
659.0
670.2
678,1
698.1
581.9
695.7
714.9
655.7
680.5
592.6
701,5
668.3
662.4
694.2
566.8
712.7
583^9
571.1
572.8
554.3
548.7
565.2
587.9
559.5
552.7
604.5
458.3
569.8
588.2
550.8
418.2
565.9
452.7
470.8
536.7
490.7
462.7
492.8
472-8
491.7
640.0
437.0
484.5
511.0
607.8
506.0
546.3
569.1
565.9
575.0
458.2
582.7
558.4
600.8
577.0
464.9
583.8
542.2
526.8
580.7
458.0
596.3
583.9
571.1
572.8
554.3
548.7
565.2
587.9
559.5
552.7
604.5
518.7
569.8
588.2
550.8
509.3
565.9
452.7
470.8
536.7
490.7
462.7
492.8
472.8
535.2
640.0
520.1
4S4.5
511.0
607.8
607.8
546.3
569.1
565.9
575.0
458.2
582.7
558.4
600.8
577,0
464.9
583.8
542.2
526.8
580.7
458.0
596.3
400.0
461.6
474.2
422.2
385.4
444.5
470.6
444.5
455.6
503.5
398.0
466.2
279.8
445.6
437.7
397.4
338.4
361.7
431.6
370.1
354.6
354.4
375.7
377.2
518.6
418.9
392.1
381.6
415.8
507.5
442.4
47D.2
452.0
471.2
338.3
483.3
492.5
460.1
488.7
345.2
483.6
427.4
395.3
473.5
351.6
486.7
                                              D-51

-------
      SUBCHRONIC TOXICITY OF  QRTHQ-CRESOL  IN SPRAGUE DAULEY RATS
                   FEMALE FOOD  CONSUKPTION DATA  (g>
                           [Feeder  Weights]
               ANIMAL NO.   new  1   old   1  neu  2  old  2  new  3  old  3
DOSE LEVEL
50 mg/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071 '
3072
3073
3074
3075
175 rag /kg/day 3079
3080
3081
3082
3083
3084
3085
30 86
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
342
355
359
365
416
367
384
352
340
354
388
370
402
360
373
365
328
360
335
379
379
422
354
338
389
360
370
380
352
368
382
359
379
367
368
383
379
346
360
346
353
346
362
365
245.0
251.9
257.5
238.8
306.0
256.5
302.0
254.9
243.8
229.0
279.5
272.1
28S.9
250.6
265.3
257.3
218.5
262.7
232.6
272.2
276.2
302,3
258.2
223.4
267.4
263,1
249.2
269.0
238.8
264.2
277.0
239.8
281.2
262.4
267.4
252.6
285.9
226.6
209.9
224.0
235.4
233.3
248.9
227.5
608.0
564.8
606.4
589.9
641.0
575.1
603.3
607.6
566.4
618.4
587.5
600.9
600.5
564.1
575.6
602.4
581.2
593.1
553.8
573.8
601.3
574.3
551.6
518.7
562.2
588.2
548.3
588.0
569.7
533.8
606.0
600.4
578.2
573.8
565.0
583.7
565.3
575.1
579.6
575.9
616.9
532.4
590.5
569.9
484.2
4843
453.2
486.4
466.8
444.0
501.2
491.9
477.4
463.9
461.8
486.9
43B.2
475.1
450.0
477.0
428.2
494.1
446.8
466.8
499.8
483.0
447.9
474.9
483,6
424.5
465.9
460.3
421.3
489.6
489.6
479.1
477.9
464.5
458.2
457.8
458.5
460.1
461.3
505.1
488.6
417.0
485.2
445.4
484.2
484.3
453.2
486,4
466.8
444.0
501.2
491.9
477.4
505.9
461.8
486.9
519.5
475.1
450.0
477.0
428.2
494.1
446.8
446.8
499.8
483.0
447.9
474.9
483.6
424.5
465.9
460.3
421.3
489.6
421.6
479.1
477.9
464.5
458.2
457.8
458.5
460.1
461.3
505.1
488.6
417.0
485.2
445.4
336.4
369,3
330,2
361,5
333,2
317,6
396.9
375.9
367.3
364.1
346.8
379.4
399.4
356.6
360.8
339.8
269.4
393.6
345.3
361.0
412.6
394.8
357.1
290.7
355.0
390.9
316.4
347.7
317.3
312.1
382.2
341.1
381.4
372.8
356.3
343,0
359.9
350.4
367.2
278.6
381.0
380.7
325.9
338.9
                                           D-52

-------
     SU3CHSONIC TOXICITY OF ORTHO-CRESOL IN SPRACUI DAULEY RATS
                FEMALE FOOD CONSUMPTION DATA Cg)
                       [Feeder Weights]
            ANIMAL  NO.  new  1  old  1  new  2  old  2  new  3  old  3
DOSE LEVEL
600 mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
385
358
386
387
354
386
399
371
375
na
389
350
378
370
380
393
363
356
404
395
406
342
351
398
380
391
364
398
364
372
301.8
269.6
278,6
278.2
254.6
275.6
309.7
270.9
277.7
na
292.0
263.8
284. 1
289.9
2B4.4
na
258,3
244.8
336.2
301.2
317.8
256.9
270.7
305,8
271.5
286.5
276,4
294.6
280.3
233.3
589.1
555.3
593.1
570.1
151.8
567.3
582.1
619.3
590.9
na
584.8
556.2
543.2
592.6
615.5
na
578,4
535.7
589.0
603.1
610.8
546.1
549.7
567.2
582.6
588.7
586.9
579.9
595.7
640.8
486.4
458.4
484.6
452.0
446.1
450.4
490.9
492.5
482.7
na
475.5
463.3
444.2
501.2
510.3
na
480,7
412.1
490.5
503.7
511.4
443.3
480.3
472.9
456.3
538.5
585.2
464.1
502.1
510.7
486.4
458.4
484.6
452.0
446.1
450.4
490.9
492.5
482.7
na
475.5
463.3
444.2
501.2
510.3
na
480,7
412.1
490.5
503.7
na
na
480.3
472.9
456.3
na
na
464.1
502.1
510.7
na
384.0
390.4
353.2
349.5
343.0
404,4
401.3
402.4
na
na
na
350.1
271.5
415.6
na
387.8
307.4
404.9
na
na
na
na
383.8
348.4
na
na
362.3
na
390.6
na = no  data  available.
                                  D-53

-------
       SUSCHRCNIC TOXICITY OF ORTHO'CRESOL  IN  SPRAGUE DAUIEY RATS
                    FEMALE FOOD CONSUMPTION DATA  (g)
                            [Feeder Heights]
                ANIMAL NO.   new  4  old  4   new  5  old  5  new  6  old  6
 DOSE LEVEL
 0 ing/kg/day
50 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
302Z
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
438.3
422.3
421. 0
425.9
430.6
426.2
426.4
424.4
422.9
427.6
419.6
420.0
439.8
420.0
423.5
428.7
422.8
424.6
440.8
426.6
421.2
423.9
422.9
425.1
441.9
421.9
423.0
431.3
423.5
452.0
458.5
453.4
424.7
446.8
417.8
425.1
425.6
421.5
436.4
416.6
437.4
410. 8
435.1
432.7
422.4
419.8
313.3
306.4
326.3
259.9
274.8
311.8
313.1
313.3
312.5
315.4
310.2
322.5
269.9
304.8
292.7
312.8
306.2
320.8
335.9
300.8
312.7
319.6
318.3
320.9
306.0
311.0
312.8
306.9
325.4
348.4
356.9
352.7
317.8
336.9
307.4
320.4
309.5
323.4
343.2
234.8
340.6
302.7
303.9
331.2
321.7
309.2
526.4
497.1
467.6
509.6
494.2
471.1
467.2
490.5
502.1
501.3
470.9
487.2
481.9
467.0
478.5
470.9
479.8
494.3
491.2
481.8
491.4
482.7
490.5
472.8
495.2
475.6
457.4
464.1
468.0
470.7
466.5
461.8
469.2
468.9
467.9
454.2
451.8
474.1
460.2
445.6
494.4
481.3
467.3
466.8
469.2
495.8
406^5
356.5
364.2
380.6
355.0
356.4
349.6
378.2
394.6
408.1
354.3
389.6
282.3
370.9
343.0
363.4
361.1
396.4
387.5
355.6
396.5
374.0
390.2
372.8
370.4
362.9
332.2
347.6
365.2
373.3
368.2
358.8
349.3
257.7
357.2
350.0
346.1
379.0
363.7
330.8
395.6
360.9
346.7
358.8
368.5
377.4
494.5
470.8
450.2
485.1
471.0
482.9
480.8
475.5
452.2
463.1
450.4
478.6
503.8
480.3
431.0
453.1
448.7
470.3
476.7
464.9
487.0
481,2
495.1
485.3
513.3
469.7
467.5
485.4
483.5
455.5
468.9
480.3
456.7
514.6
476.4
479.9
473.3
465.7
466.2
460.1
505.2
479.0
449.0
499.9
471.2
491.4
385.7
361.7
345.6
341.5
319.4
377.9
373.5
355.6
349.7
365.6
341.3
375.0
314.9
282.9
296.9
339.3
323.7
373.4
365.0
342.0
381.0
375.5
393.4
392.2
394.1
355.1
352.6
362.0
376.3
352.6
372.6
377.7
337.4
418.1
365.0
396.6
364.3
369.6
359.0
319.2
397.9
364.4
322.5
388.1
360.5
381.3
                                        D-54

-------
      SUBCHRQN1C TOXICITY OF  ORTHO-CRESOL  IN SPRAGUE DAWLEY RATS
                   FEMALE FOOD  CONSUMPTION DATA (g)
                           [Feeder Weights]
               AHIHAL  NO-   new   4  old  4  new  5  old  5  new  6  old  6
DOSE LEVEL
50 mg/kg/day 3062
Ccontinued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
423
419
415
424
435
442
422
420
415
424
419
414
423
414
448
469
441
446
476
479
448
441
463
433
431
433
406
456
431
437
480
449
466
466
439
413
444
443
441
420
434
431
431
438
.6
.4
.4
.0
.2
.8
.6
.1
.7
.9
.3
.4
.9
.0
.0
.9
.9
.8
.2
.7
.5
.4
.8
.6
.1
.0
.0
.3
.5
.3
.7
.2
.7
.7
.6
.4
.8
.1
.0
.9
.8
.9
.6
.4
320
.6
309.3
309
288
332
296
325
302
233
298
311
303
292
292
315
350
286
340
360
371
353
350
369
326
305
347
295
348
295
328
370
348
366
366
338
282
336
318
341
209
313
320
366
322
.8
.4
,6
,9
,7
.2
.7
,9
,3
.2
.5
.5
.4
.8
,5
.2
,0
.2
.2
.3
.0
.6
.3
.5
.7
.6
.0
.4
.6
.7
.3
.8
.1
.2
.8
.8
.1
.7
.2
.2
.0
.9
485.
443.
463.
456.
478.
459.
453.
472.
474.
467.
452.
448.
447.
483.
546.
469.
477.
494.
454.
469.
440.
471.
478.
440.
422.
439.
418.
459.
423.
461.
481.
410.
442.
423.
431.
440.
429.
421.
446.
423.
414.
412.
447.
423.
8
2
1
0
6
a
4
3
0
9
5
2
4
5
4
9
3
2
1
9
4
0
6
5
9
2
1
5
7
4
9
4
4
8
0
9
9
9
7
8
5
4
3
3
366.2
333
351
318
368
335
365
354
359
348
346
350
319
361
432
362
33"0
399
332
361
346
382
388
333
307
349
303
337
274
351
371
305
341
318
317
318
327
312
355
246
302
311
337
297
.1
.5
.6
.3
.4
.5
.9
.2
.3
.9
.7
.3
.9
.8
.2
.8
.7
.8
.4
.0
.0
.7
.2
.7
.5
.4
.9
.9
.5
.8
.3
.2
.8
.7
.7
.3
.3
.3
.5
.4
.9
.8
.9
482.4
467
474
465
496
470
464
488
488
479
455
496
465
474
476
469
464
475
472
492
458
481
489
481
453
493
457
485
471
485
473
455
454
487
483
471
473
497
481
485
517
443
483
501
.2
.9
.8
.5
.9
.8
.4
.2
.2
.5
.4
.1
.8
.6
.6
.9
.5
.6
.8
.9
.5
.2
.2
.6
.8
.7
.7
.8
.9
.6
.0
.6
.5
,8
.5
.4
.0
.6
.6
.5
.0
.7
.1
367.7
351.5
361.0
324.3
383.3
350.7
. 372.2
363.6
364.7
349.7
343.4
392.9
322.8
344.1
376.7
363^2
333.9
371.9
355.4
372.8
355.7
375.7
389.8
380.5
332.3
402.1
340.5
358.0
363.5
373.5
369.5
355.3
351.5
381.2
373.8
343.1
374.1
379.1
381.7
324.5
393.8
375.3
389.1
373.0
                                      D-55

-------
         SUBCHRON1C TOXICITT OF ORTHO-CRESOL IN  SPRAGUE  DAULEY RATS
                     FEMALE FOOD CONSUMPTION DATA (g)
                            [Feeder Weights]
                 ANIMAL NO,   new  4  old  4  new  5  old  5  new  6  old  6
    DOSE LEVEL
6DO mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
438,9
434.0
426.8
433.3
415.0
443.9
430.2
457,2
na
na
na
462,2
418.3
423.8
na
419.9
430.4
425.5
na
na
na
na
415.4
425.4
na
na
428.1
na
' 432.7
na
342.7
326.1
312.7
334.2
293.2
348.4
327.7
357.2
na
na
na
355.6
321.4
303.2
na
326.5
266.9
327.5
na
na
na
na
324,3
307.7
na
na
308.0
na
294.3
na
427.8
428.6
406.0
407.2
435.2
441.1
424.1
451.8
na
na
na
439.1
428.6
398,6
na
405.5
437,2
417.9
na
na
na
na
430.8
433.9
na
na
409.1
na
410.7
na
333.9
329.9
293.5
305.9
347.3
351.6
327.8
362.2
na
na
na
341.2
333.5
na
na
304.6
302.0
312.8
na
na
na
na
322.4
315.6
na
na
291.1
na
268.3
na
na
475.2
470.0
484.9
474.3
476.0
451.5
470.6
na
na
na
na
na
na
na
464.2
463.6
464.0
na
na
na
na
445.9
489.7
na
na
506.2
na
na
na
na
367.0
377,!
379.3
333.4
389,1
352,6
361.3
na
na
na
na
na
na
na
356,5
237,6
365,7
na
na
na
na
351.1
394.2
na
na
390,3
na
na
na = no  data  available.
                                         D-56

-------
        SU3CHRQNIC  TOXIClTf  Of ORTH -CRESOL IN SPRAGUE DAULEY RATS
                   FEMALE  FOOD CONSUMPTION DATA (g)
                           [Feeder Weights]
                ANIMAL NO.  new  7  old  7  new  8  old  8  new  9  old  9
  DOSE LEVEL;
0 mg/kg/day 3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
50 mg/kg/day 3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
385.7
361.7
370.3
341.5
368.1
377.9
373.5
355.6
349.7
365.5
442.8
506.5
433.4
474.0
483.9
432.2
432.7
473.8
477.8
434.0
455.4
450.3
476.8
451.2
470.4
418.2
447.1
434.3
428.6
460.8
405.3
377.7
367.8
418.1
365.0
396.6
391.8
369.6
359.0
424.6
566.0
50t. 2
469.4
515.5
454.3
487.9
358.8
337.9
339.9
310.2
329.2
344.9
344.7
327.3
322.4
346.8
345.7
414.6
278.8
380.8
361.1
338.3
342. 2
388.3
386.1
330.9
354.2
356.8
383.9
367.0
356.4
325.6
341.7
338.3
336.6
369.5
350.7
374.4
325.6
321.7
376,9
348.9
370.8
358.1
343.1
393.7
471.6
390.1
373.8
414.6
356.1
391.0
na
na
na
na
na
na
na
na
na
na
441.6
463.3
422.4
459.3
441.1
426.0
412. 1
434.6
460.7
422.6
428.1
424.1
420.0
420.9
442.2
414.3
425.5
401.6
412.6
428.8
na
na
na
na
na
na
na
na
na
na
471.6
424.4
430.2
433.3
435.3
440.9
na
na
na
na
na
na
na
na
na
na
348.3
381.9
292.6
367.0
322.0
331.7
311.6
348.5
358.4
308.2
335.6
331.2
321.3
336.4
327.7
318.3
327.1
308.6
318.7
338.7
na
na
na
na
na
na
na
na
na
na
382.7
314.3
307.6
328.5
346.3
346.6
na
na
na
na
na
na
na
na
na
na
443.8
452.1
480.6
452.4
434.6
467.1
442.1
429.3
449.2
450.1
460.1
510.8
490.4
444.7
463.1
479.0
440.1
436.8
445.6
437.8
na
na
na
na
na
na
na
na
na
na
466.3
442.1
455.9
463.2
455.6
421 .B
na
na
na
na
na
na
na
na
na
na
349.8
367.2
314.4
348.0
315.5
363.5
339.9
348.7
352.8
340.3
358.1
424.6
396.8
352.2
363.3
387.9
340.5
337.3
356.3
344.4
na
na
na
na
na
na
na
na
na
na
377.1
313.8
332.8
352.2
362.5
316.7
na = no  data  available.
                                       D-57

-------
     SUBCHRON1C TOXtClTY OF ORTH -CRESOL JN SPRAGUE DAULEY RATS
                 FEMALE FOOD CONSUMPTION DATA (i)
                        [Feeder Weights]
             ANIMAL  NO.  new  7  old  7  new  8  old  8  new  9  old  9
DOSE  LEVEL
50 mg/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3Q83
3084
3085
3086
3087
3088
3039
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
31 D6
3107
3108
444.
2
437.7
461.
432.
480.
478.
456.
1
6
5
1
6
461 .9
474.
462.
474.
467.
434.
441.
446.
363.
333.
371.
355.
372.
355.
375.
389.
380.
452.
455.
443.
462.
451.
434.
465.
428.
445.
461.
455.
434.
442,
472.
467.
425.
449.
6
9
1
3
8
1
1
2
9
9
4
8
7
7
8
5
1
3
0
8
B
5
6
6
1
9
8
1
7
7
6
2
1
451.8
437.
450.
1
4
337.2
334
351
310
374
356
369
347
364
364
371
376
324
325
414
330
294
349
322
332
356
347
322
352
365
372
345
354
356
345
361
342
355
366
363
321
359
371
373
328
352
368,
359,
342,
.6
.3
,6
.3
.4
.3
.8
.3
.9
.2
.9
.1
.5
.7
.1
.7
.9
.4
.1
.9
.4
.0
.4
.8
.3
.9
.9
.5
,2
.9
.2
.2
.9
.6
.9
.2
.3
.2
.2
.9
.3
.9
.2
419
413
416
406
415
408
415
419
418
416
41Z
416
421
413










425
420
422
413
434
443
475
423
432
.431
430
415
424
439
438
428
.6
.1
.3
.4
.a
,2
.1
.5
.0
.2
.7
.5
.3
.1
na
na
na
na
na
na
na
na
na
na
.6
.9
.3
.2
.7
.3
.9
.1
.7
.2
.1
.3
.9
.9
.9
.7
428.3
432.2
429.6
421.3
320
3n
322
280
.9
.,9
.8
.6
318.5
290
329
303
279
308
.8
.4
.3
.0
.8
384.7
318
325
309










329
.4
.4
.5 "
na
na
na
na
na
na
na
na
na
na
.2
337.1
325
299
338
342
382
335
346
341
328
296
338
331
354
320
317
330
343
305
.4
.5
.3
.3
.0
.3
.8
.2
.4
.2
.7
,0
.8
,2
.4
.1
.0
.3
458.5
443,5
407.7
417.2
411.0
417.2
428.5
410.5
438.9
412.4
411.8
418.7
382.6
419.5
na
na
na
na
na
na
na
na
na
na
502.9
497.9
492.0
530.9
534.7
515.7
505.1
517.9
503.4
527.9
478.5
427.2
510.8
471.0
530.2
492.1
496.5
525.0
483.3
453.0
354
345
307
282
309
298
342
290
309
287
308
317
269
302










.9
.3
.2
.6
.9
.1
.3
.3
.9
.9
.5
.8
.0
.9
na
na
na
na
na
na
na
na
na
na
396.9
410
.0
37S.7
419
419
423
365
423
412
400
373
416
416
367
465
365
387
420
393
339
.5
.7
.8
.4
.6
.1
.1
.6
.8
.0
.3
.6
.5
.2
.3
.7
.9
 na  =  no  data  available.
                                     D-58

-------
     SUBCKRONiC TOXICITY OF ORTH -CRESOL IN SPRAGUE DAULEY RATS
                FEMALE FOOD  CONSUMPTION DATA 
-------
                  SUBCHRON1C TOXICITY OF QRTHO-CRESOl IN  SPRACUE DAULEY RATS
                              FEMALE FOOD CONSUMPTION DATA 
-------
                SUBCHRON1C TOX1CITY OF ORTKO-CRESOL  IN SPRAGUE DAWLEY RATS
                            FEMALE FOOD  CONSUMPTION DATA (g)
                                   [Feeder Weights)
             ANIMAL NO.  new  10  old  10  ney  11  old  11  ney  12  old  12  new  13  old  13
DOSE  LEVEL
50 mg/'tcg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
1093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
437. Z
445.4
423.8
411.9
424.5
421.1
426.7
425.7
431.0
432.2
422.4
422.5
415.1
434.3
na
na
na
na
na
na
na
na
na
na
452.8
428.3
422.7
416.0
449.0
423.8
426.2
452.9
448.8
435.1
448.8
432.3
436.1
456.9
448.2
461.6
460.8
424.2
434.0
425.1
328.0
342.7
319.5
308.2
320.2
292.5
336.4
298.9
317,4
317.0
316.4
320.6
296.5
311.8
na
na
na
na
na
na
na
na
na
na
348.3
358.8
331.4
310.0
253,2
323.7
333.3
356.1
376.5
346. 0
351.1
325.3
351.9
357.0
353.1
329.0
357.5
324.7
340.2
321.9
439.3
437.1
427.2
432.5
432.4
436.4
430.2
432.8
430.9
432.1
434.2
433.1
428.6
432,0
na
na
na
na
na
na
na
na
na
na
428.8
425.0
427.4
426.5
435.5
432.1
423.4
425.9
426.3
426.9
426.2
426.7
424.3
426.6
425.3
429.7
427.8
427.5
425.6
425.9
331.5
336.3
329.3
309,1
339.5
325.1
339,6
310.0
325. 4
319.2
329.2
353.1
309. 5
306. 3
na
na
na
na
na
na
na
na
na
na
336.9
355,9
331.2
310.8
321.8
332.1
262.5
337.8
350.8
330.1
332.6
309.9
337.8
326.5
327.8
304.7
334.5
333.4
338.0
332.8
459.8
430.9
422.0
425.6
446.4
428.6
440.8
453.7
438.8
454.2
440.8
456.6
444.4
461.4
na
na
na
na
na
na
na
na
na
na
425.9 ,
439,3
455.2
445.6
447,9
432.7
458.3
446.7
422.8
462.8
452.5
443.2
468.6
447,0
482.1
434.2
467.1
476.4
458.8
434.7
361.1
338. 3
318. 0
305.8
346.6
313,5
356.2
347.2
329.2
336.6
341.4
381.2
330.7
341.2
na
na
na
na
na
na
na
na
na
na
331.1
363.9
355.0
355.6
336.3
324.7
366.1
381.1
310.4
374.7
335.7
364.5
377.9
346.9
392.0
306.9
366.2
379.8
365.4
331.2
409.2
444,5
452.3
431.0
435.2
453.4
422.5
441.5
426.9
441.8
476,2
483.1
494.1
488.3
na
na
na
na
na
na
na
na
na
na
412.3
459.2
456.1
451.0
472.5
459.6
445.4
455.1
482.4
455.3
541.3
548.2
522.6
448.5
543.1
506.2
568.3
508.3
442.8
416.1
321.0
354.6
352.2
306,7
335.5
329.4
336.7
330.5
315.2
317.0
371,8
385.4
364.7
376.7
na
na
na
na
na
na
na
na
na
na
318.4
378.7
369.1
349.7
368,2
378.7
366.5
371.7
389.6
376.0
432.0
452.8
433.2
342.9
462.8
397.9
482.2
424.7
351.8
329.5
 na - no  data available.
                                          D-61

-------
              SUBCHRCNIC TQXICJTY OF QRTHQ-CRESQL IN SPRAGUE DAULEY RATS
                          FEMALE FOOD CONSUMPTION DATA (g)
                                 [Feeder Weights]
           ANIMAL NO.  ney  10  old  10  n«y  11  old  11  new  12  old  12  ney  13  old
DOSE LEVEL _______ _ . .
600 mg/kg/day ' 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
312?
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
415.5
414.4
427.8
na
na
na
na
418.4
410.9
na
na
400.3
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
318,9
300.4
340,6
na
na
na
na
331.9
292.4
na
na
295.8
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
420.4
416.9
423.2
na
na
na
na
421.5
413.2
na
na
422.2
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
319.6
308.5
335.0
na
na
na
na
331.9
290.7
na
na
316,4
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
421.9
431.9
439.6
na
na
na
na
453.4
420.2
na
na
439.5
na
na
na
na
• na
na
na
na
na
na
na
na
na
na
na
na
na
na
320.4
314.5
350.3
na
na
na
na
356.9
321.8
na
na
332.8
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
423.3
432.3
412.1
na
na
na
na
438.9
471,5
na
na
465.2
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
348.4
325.4
341.9
na
na
na
na
370.1
383.6
na
na
376.7
na
na
na = no  data available.
                                       D-62

-------
          SUBCHRONiC TOXIC1TY OF OSTHO-CRESOL IN SPRAGUE  DAWLEY RATS
                           MALE HEMATQLQGY VALUES
                             [Interim Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
ANIMAL NO.        RiC         HGB
            (x 1Q*6/mnf3)  (g/dl)
HCT    PT     APTT    RETIC
     (sec.)   (see.)  (% rbc)
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2881
2882
2883
2884
2885
2886
2887
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
8.16
7.91
7,89
7.13
7.47
7.95
7.63
8.27
7.98
6.27
7.79
8.89
8.85
8.79
8.18
7.76
7.55
7.44
7.64
8.08
8.07
8.52
8.32
7.80
7.63
7.81
7.74
7.70
7.96
7.82
7.64
7.91
7.83
7.13
dead
7.28
7.43
8.18
7.60
8.79
15.7
16.1
16.2
15.2
14.9
15.6
14.7
16.0
15.7
15.7
15.2
17.3
17.0
16.1
15.8
14.7
15.0
14.8
15.0
16.1
15.4
15.8
16.3
15.3
14.5
15.4
15.3
15.4
15.0
15.6
14.8
15.5
15.1
14.8
dead
15.9
15.0
15.9
14.6
16.1
42.6
44.3
46.7
40.7
41.0
44.1
40.6
45.5
45.6
43.7
43.0
48.8
45.5
48.5
43.1
40.4
43.6
40.5
43.0
46.1
44.1
46.0
47.3
42.5
42.2
43.6
44.9
44.5
43.9
45.0
42.4
43.1
44.5
41.0
dead
45.1
42.5
46.3
42.3
47.0
11.9
11.0
10.9
12.5
12.3
11.5
11.6
11.9
12.2
12.3
12.0
13.3
13.0
11.1
13.3
11.5
10.3
11.6
10.4
10.9
11.7
11.8
13.0
11.4
11,8
Z
10.5
13.0
12.4
11.7
11.8
11.5
12.0
12.2
dead
10.3
10.7
11.3
11.4
11.3
28.8
30.9
29.3
31.5
30.6
33.6
30.9
28.8
34.0
27.9
30.9
35.3
34.9
34.5
33.2
31.1
35.1
28.1
39.0
37.0
34.7
29.0
35. Z
31.5
30.3
2
35.2
35.9
33.5
30.7
30.6
30.7
34.9
31.0
dead
36.3
30.3
30.7
34.0
34.6
0.9
0.9
1.0
0.8
0.9
0.6
1.0
0.5
0.9
1.6
0.8
0.4
0.9
0.9
0.1
1.2
1.3
0.5
0.6
0.1
0.5
0.5
0.2
• 1.4
1.3
0.1
1.0
1.5
0.5
0.6
2.0
0.5
0.8
0.2
dead
0.4
0.7
1.8
0.3
0.8
                                                 D-63

-------
             SUSCHRONtC TOXICITY OF ORTHO-CRESOL  IN SPRAGUE DAWIEY  PATS
                              MALE HEMATQLQGY VALUES
                                [Interim Sacrifice]
               ANIMAL NO.
                               UBC
 DOSE LEVEL
 0 mg/kg/day
 SEGS    SANDS    LYMPHS    MONO     EOS
% wo  <% WBO  c% wso  c% wso  <% weo
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2881
2882
2883
2884
2885
2886
2837
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
. 2951
295 Z
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
13.4
12.9
17.1
19.9
16.7
18.9
17.1
22.8
15.0
13.0
11.7
16.8
16.2
14.4
9.4
15.3
14.7
11.8
13.3
22.5
12.4
11.6
15.8
17.5
15.5
14.5
12.5
18.2
14.6
9.4
16.3
13.0
15.1
18.2
dead
11.7
14.4
17.8
12.2
14.1
3
6
6
9
8
6
18
10
5
10
7
6
18
2
6
8
9
13
11
15
7
15
8
6
15
22
9
15
6
12
20
12
19
10
dead
16
11
4
15
7
0
0
0
1
2
0
0
0
0 .
0
0
3
1
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
1
0
0
0
dead
0
0
0
1
0
95
92
94
89
89
92
79
90
90
90
90
90
80
94
89
83
87
83
85
85
85
83
92
89
77
74
87
83
92
87
76
86
77
85
dead
80
85
95
83
91
1
1
0
1
1
1
1
0
4
0
Z
1
1
0
5
4
4
1
2
0
5
2
0
5
2
3
3
0
1
1
3
1
1
5
dead
3
4
0
0
1
1
1
0
0
0
1
2
0
1
0
1
0
0
4
0
4
0
3
2
0
3
0
0
0
0
1
0
2
1
0
0
1
3
0
dead
1
0
' 1
1
1
                                             D-64

-------
                            SUSCHRONIC  TOXIC1TY  OF  QRTHC-CRESCL  IN  SPRAGUE  PAWUY  RATS
                                               MALE  HEMATOLOGY  VALUES
                                                 [Interim Sacrif ice]
 DOSE LEVEL
 0 mg/kg/day
ANIMAL NO.       UBC            SEGS          BANDS
            (x 10A3/imr"3>   Cx 10*3/nnT3>   Cx  10*3/nrrr3)
                                                                              LYMPHS
                                                                                              MONO
                                                                                                             EOS
50 rog/kg/day
175 mg/kg/day
600 mg/ltg/day
                                                                                                        (x
2881
2882
2883
2884
2885
2886
28S7
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
13.4
12.9
17.1
19.9
16.7
18.9
17.1
22.8
15.0
13.0
11.7
16.8
16.2
14.4
9.4
15.3
14.7
11.8
13.3
22.5
12.4
11.6
15.8
17.5
15.5
14.5
12.5
18.2
14.6
9.4
16.3
13.0
15.1
18.2
dead -
11.7
14.4
17.8
12.2
14.1
0.4
o.a
1.0
1,8
1.3
1.1
3.1
2.3
0.8
1.3
0.8
1.0
2.9
0.3
0.6
1.2
1.3
1.5
1.5
3.4
0.9
1.7
1.3
1.1
2.3
3.2
1.1
2.7
0.9
1-1
3.3
1.6
2.9
1.8
dead
1.9
1.6
0.7
1.8
1.0
0.0
0.0
0.0
0.2
0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.5
0.2
o.o
0.0
0.2
0.0
0.0
0.0
0.0
o.o
o.o
0.0
0.0
o.o
0.0
0.1
0.0
0.0
0.0
0.2
0.0
0.0
0.0
dead
0.0
0.0
o.o
0.1
0.0
12.7
11.9
16.1
17-7
14.9
17.4
13.5
20.5
13.5
11.7
10.5
15.1
13.0
13.5
8.4
12.7
12.8
9.8
11.3
19.1
10.5
9.6
14.5
15.6
11.9
10.7
10.9
15.1
13.4
8.2
12,4
11.2
11.6
15.5
dead
9.4
12.2
16.9
10.1
12.8
0.1
0.1
0.0
0.2
0.2
0.2
0.2
0.0
0.6
0.0
0.2
0.2
0.2
0.0
0.5
0.6
0.6
0.1
0.3
0.0
0.6
0.2
0.0
0.9
0.3
0.4
0.4
0.0
0.1
0.1
0.5
0,1
0.2
0.9
dead
0.4
0.6
0.0
0.0
0.1
0.1
0.1
0.0
0.0
0.0
0.2
0.3
0.0
0.2
0.0
0.1
0.0
0.0
0.6
0.0
0.6
0,0
0.4
0.3
0.0
0.4
0.0
0.0
0.0
0.0
0.1
0.0
0.4
0,1
0,0
c.o
0.1
0.5
0.0
dead
•0.1
0.0
0.2
0.1
0.1

-------
          SUBCHRONIC  TOXICITY OF ORTHQ-CRESQL IN SPRAGUE DAWLEf RATS
                           MALE HEMATOLQGY VALUES
                             [Terminal Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.

2891
2892
2893
2894
2895
2896
2897
2898
2399
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2963
2966
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
RBC
(x 10'6/nrT3)
8.26
8.90
8.65
8.67
8.71
8.35
8.70
8.27
9.09
8.62
8.65
8.23
8.88
9.30
8.36
8.02
8.78
8.89
8.18
8.23
8.24
8.05
8.54
8.49
8.19
9.43
9.35
8,58
8.25
8.60
8.72
7,88
dead
dead
8.20
dead
9.43
dead
8.15
9.11
HGB
(g/dl)
15.0
15.5
15.8
16.0
15.0
15.3
14.8
15.0
15.2
14.9
15.5
15.4
15.5
16.0
14.8
14.7
15.0
15.1
15.3
14.6
15.4
15.0
15.6
15.4
14.3
16.4
15,5
15.3
14.9
15.9
15.5
15.2
dead
dead
14.8
dead
16.0
dead
14.9
16.0
HCT
C/.)
43.2
44.1
45.4
45.0
41.0
43.4
42.8
42.6
43.7
41.6
43.6
43.7
41.9
46.4
41.4
43.3
42.3
44.8
42.2
39.6
44.0
42.8
44.7
43.1
42.5
47.5
45.2
42.5
42.8
46.1
44.6
43.7
dead
deed
41.6
dead
46.8
dead
42.6
44.4
PT
(sec.)
14.4
11.2
10.2
8.6
9.9
11.6
6. a
9.7
12.6
11.8
11.0
11.6
11.6
11.3
11.9
11.5
6.8
11.3
11.7
12.5
12.4
12.4
12.2
11.8
11.3
11.4
12.1
12. 7
13.8
11.7
15.1
14.4
dead
dead
11.1
dead
8.6
dead
8.1
6.8
APTT
Csec.)
44.6
34.0
34.2
27.5
33.9
3D. 5
38.0
31.6
35.5
34.5
29.3
34.3
32.3
33.0
35.8
38.3
33.1
36.1
33.0
33 .3
37.7
36.3
34.8
31.6
32.5
32.2
18.2
34.8
37.7
33.4
34.2
35.1
dead
dead
33.4
dead
35.2
dead
10.3
32,4
RET1C
(54 rbc)
1.1
1.1
0.8
1.1
0.6
1.1
0.4
0.5
1.8
1.0
0.5
0,9
0.4
0.4
1.1
0.7
0.5
1.9
3,3
1.2
2.7
2.1
1.6
3.0
0.7
0.3
0.8
0.5
1.6
1.7
0.5
0.5
dead
dead
4,0
dead
1.0
dead
0.2
1.9
                                              D-GG

-------
             SUBCHRONIC TOXICiTY OF ORTHO-CRESOL  IN  SPRAGUE DAWLEY RATS
                               MALE HEMATOLOGY VALUES
                                [Terminal  Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
ANIMAL NO,       WBC         SECS
            (x 10A3/imT3)   (% U8C)
BANDS    LYMPHS    MONO      EOS
  WBC)  (% WBC)  (% WBC)   (% WBC)
50 mg/kg/day
175 rag/kg/day
600 mg/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
15.4
10.4
13.6
16.2
16.4
11. B
13.8
14,6
17.1
13.9
9.5
9.9
14.8
11.3
15,2
11.5
17.8
13.0
11.3
11.5
11.5
13.4
13.4
14.1
11.2
16.6
16.1
11.2
15.1
17.8
13.5
11.1
dead
dead
12.4
dead
11.9
dead
16.5
20.0
5
18
11
43
21
9
14
16
34
17
8
19
33
21
16
9
13
24
15
14
28
13
13
22
34
9
20
11
17
18
32
2
dead
dead
12
dead
24
dead
10
11
o.
0
0
1
1
1
2
0
0
1
0
0
1
0
2
0
1
1
1
0
0
0
0
2
1
0
0
0
0
0
1
1
dead
dead
0
dead
0
dead
0
1
92
80
89
54
77
88
82
80
63
79
88
72
61
78
76
85
84
73
75
84
70
82
84
74
62
88
79
85
77
81
65
84
dead
dead
85
dead
71
dead
87
65
3
0
0
1
1
2
2
1
2
1
3
9
5
0
6
5
3
1
9
2
2
3
3
2
1
1
1
2
6
0
1
12
dead
dead
3
dead
3
dead
3
2
0
1
0
1
0
0
0
3
1
2
1
0
0
1
0
1
0
1
0
0
0
2
0
0
1
2
0
2
0
1
1
1
dead
dead
0
dead
2
dead
0
1
                                      D-G7

-------
                            SUBCKROHIC TOXIC1TY Of ORTHO-CRESQL  IN  SPRAGUE DAWLEY RATS
                                              HALE KEHATOLOGY  VALUES
                                               [Terminal  Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.

2391
2892
2893
2894
2895
2396
2897
2898
2899
2900
2924
2925
2926
2927
2928-
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
wee
(x 10A3/mniA3)
15.4
10.4
13.6
16.2
16.4
11.8
13.8
14.6
17.1
13.9
9.5
9.9
14.8
11.3
15.2
11.5
17.8
13.0
11.3
11.5
11.5
13.4
13.4
14.1
11.2
16.6
16.1
11.2
15.1
17.8
13.5
11.1
dead
dead
12.4
dead
11.9
dead
16.5
20.0
SEGS
(x 10A3/iTfnA3
0.8
1.9
1.5
7. a
3.4
1.1
1.9
2.3
5.8
2.4
0.8
1.9
4.9
2.4
2.4
1.0
2.3
3.1
1.7
1.6
3.2
1.7
1.7
3.1
3.8
1.5
3.2
1.2
2.6
3.2
4.3
0.2
dead
dead
1.5
dead
2.9
dead
1.7
2.2
BANDS
) (x 1QA3/(imA3
0.0
0.0
0.0
0.2
0.2
0.1
0.3
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.3
0.0
0.2
0.1
0.1
0.0
0.0
0.0
0.0
0.3
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.1
dead
dead
0.0
dead
0.0
dead
0.0
0.2
LYMPHS
3 
-------
          SUBCHRONtC TOXICITY QF ORTHO-CRESOL  IN SPRAGUE DAULEY RATS
                           FEMALE HEMATOLQGt VALUES
                              [Interim Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 (Tig/kg/day
600 mg/kg/day
ANIMAL NO,

3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
RBC
8.18
7.79
7.84
8.01
7.92
7.97
8.33
7.79
8.20
7.79
8.28
7.70
7.99
3.18
7.83
7.28
8.42
7.67
.b
7.62
7.95
7.50
7.97
7.29
8.30
7.50
6.75
7.89
7.23
7.14
dead
dead
7.74
.a
7.90
7.59
8.12
7.15
7.79
dead
HGS
S3 (g/dl)
15.5
15.4
15.8
15.9
15.5
15,9
16,2
15.4
14.8
15.4
15.5
15.0
15.9
16.6
16.0
14.3
16.9
15.8
.b
15.5
16.2
15.8
14.8
14.9
16.2
15.1
14.6
14.8
15.8
14.9
dead
dead
15.1
,a
15.4
15.2
15.7
14.8
15.4
dead
HCT
43.5
43.5
44.3
45.8
44.5
45.0
46.8
43.7
42.2
43.2
44.2
42.2
45.8
44.6
44.4
39.8
46.2
40.0
.b
45.0
45.7
43.1
37.3
40.9
44.8
41.7
39.0
43.2
40.7
40,1
dead
dead
42.2
.a
44.4
43.2
44.5
41.1
43.5
dead
PT
Csec.)
10.0
10.7
11.4
11.2
11.0
11.1
12.1
10.8
10.3
11.2
10.3
11.5
11.5
11.2
10.7
10.9
10.8
10.6
10.3
9.6
10.9
11.6
8.0
11.3
11.0
11.2
11.4
11.3
10.3
12.1
dead
dead
Z
11.9
10.6
12.2
11.3
13.4
10.5
dead
A PIT
(sec.)
'36.6
33.7
27.3
35.7
29.3
36.2
33.3
32.9
40.1
48.1
38.3
33.7
42.8
32.0
29.4
32.5
29.8
33.2
34.8
32.7
32.6
29.9
34.2
36.5
32.8
28.2
33.0
37.0
30.5
45.4
dead
dead
Z
35.5
36.2
31.5
37.5
44.1
33.7
dead
RET1C
(% rbc)
1.6
0.4
1.2
0.7
2,3
0.3
0.1
0.9
0.1
0.1
0.1
O.T
0.6
1.8
1.0
0.7
0.5
1.0
0.7
0.3
0.7
0.5
1.5
0.5
0.7
0.8
0.5
0.7
0.3
0.1
dead
dead
4.0
.8
1.1
2.2
2.1
0.2
1.8
dead
                   88lood clotted
                   "Sample  lost
                                               D-G9

-------
   DOSE LEVEL
               SUBCHRON1C  TOXICITY OF ORTHO-CRESOL IK SPRAGUE DAWLEY RATS
                              FEMALE HEHATOLOGY VALUES
                                 [Interim Sacrifice]
ANIMAL NO.      WBC        SEGS   BANDS    LYMPHS    HOMO     EOS
           (x 1Q"3/mmA3)   (% WBC)   (% UBC)  (% UBC)  (% U8C)  (% U8C)
0 mg/kg/day









SO mg/kg/day









175 ing/kg/day









600 mg/kg/day




1




3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082'
3083
3084
3085
3086
3087
3088
3112
3113
3114
3115
3116
3117
3118
3119
•3120
3121
13.7
9.7
7.5
10.9
14.2
9.0
8,5
13.1
13.0
9.5
11.6
9.6
11.8
24.8
9.9
13.4
12.1
10.6
na
10.4
16.2
13.1
9.9
12.6
11.3
10.2
11.6
12.1
10.2
13.7
na
na
14.9
na
13.0
20.0
11.1
13.8
9.7
na
9
8
5
14
9
12
8
7
13
7
8
17
8
15
8
2
32
6
17
4
14
9
6
16
4
1
25
13
14
11
na
na
10
na
30
7
10
17
8
na
1
0'
0
0
0
2
0
• o
0
0
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
na
na
0
na
0
0
1
1
0
na
as
90
94
82
89
85
86
,92
84
90
91
76
87
83
89
97
67
90
79
91
84
83
90
82
94
93
73
86
84
88
na
na
90
na
67
91
87
81 '
91
na
4
2
1
3
2
1
1
1
2
2
0
9
2
2
3
1
0
4
2
3
0
2
0
2
1
5
1
0
2
1
na
na
0
na
3
2
1
1
1
na
1
0
0
1
0
c
5
0
1
1
0
1
3
0
1
0
0
0
0
2
1
1
4
0
1
1
0
1
0
0
na
na
0
na
0
0
2
0
0
na
na  =  no  data  available.
                                      D-70

-------
                       SUBCHRQNIC  TQX1CITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                                      FEMALE KEMATQLQGY VALUES
                                        tlnterira Sacrifice]

DOSE LEVEL
0 mg/kg/day









50 mg/kg/day









175 ing/kg/day









600 mg/kg/day









ANIMAL NO.

3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3084
3085
3086
3087
3038
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
UBC
(x 10"3/imT3) (x
13.7
9.7
7.5
10.9
14.2
9.0 •
8.5
13.1
13.0
9.5
11.6
9.6
11.8
24.8
9.9
13.4
12.1
10.6
na
10.4
16.2
13.1
9.9
12.6
11.3
10.2
11.6
12.1
10.2
13.7
na
na
14.9
na
13.0
20.0
11.1
13.8
9.7
na
SEGS
1Q*3/mT3
1.2
0.8
0.4
1.5
1.3
1.1
0.7
0.9
1.7
0.7
0.9
1.6
0.9
3.7
0.8
0.3
3.9
0.6
na
0.4
2.3
1.2
0.6
2.0
0.5
0.1
2.9
1.6
1.4
1.5
ne
na
1.5
na
3,9
1.4
1.1
2.3
0.8
na
BANDS
) (x 10*3/^3)
0,1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
D.O
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
na
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
na
na
0.0
na
0.0
0.0
0.0
0.1
0.0
na
LYMPHS

-------
          SUBCHRONIC TOXICITY  OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                           FEMALE HEMATQIQGY VALUES
                             CTerminal Sacrifice]
 DOSE LEVEL
 0 nig/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.

3023
3024"
3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3053
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3128
3129
3130
3135
3136
3139
RBC
(x 10*6/mmA2
8.36
8.77
8.67
7.97
8,56
8.73
7.75
8.28
8.07
9.19
8.55
8.48
8.52
8.20
8.65
8.30
8.43
8.33
8.43
7.69
8.18
8.56
8.00
7,54
7.94
8.41
8.75
9.06
8.27
8.36
dead
dead
9.12
8.54
8.15
7.72
HG8
i) (g/dl)
16.3
15.7
16.3
15.3
16.0
16.2
14.3
15.9
15.2
16.5
16.0
15.6
15.3
15.1
16.6
16.1
15.6
16.3
15.8
15.3
15.2
15.2
15.5
14.0
14.5
15.4
16.2
16.2
15.3
16.1
dead
dead
16.4
15.4
15.5
15.2
HCT
(%)
45.5
44.3
45.3
41.4
46.3
45.3
3S.7
44.9
41.8
46.4
44.4
43.6
43.9
42.7
46.1
45.7
44.0
45.2
44.2
41.8
41.9
41.4
43,5
40.7
41.6
44.1
45.3
47.1
42.7
44.9
dead
dead
47.2
43.3
44.5
43.5
PT
(sec.)
12.3
9.8
11.3
11.4
11.3
10.4
10.9
10.3
11.1
10.3
12.9
8.3
10.8
11.4
10.1
12.2
10.8
11.1
11.0
11.4
8.1
11.8
9,7
10.6
12.7
12.5
10.9
12.5
10.9
6.5
dead
dead
10.5
11,2
10.4
10.8
APTT
(sec.)
34.5
21.4
31.4
35.5
46.1
34.0
33.5
32,5
29.1
31.3
38.0
33.2
36,8
29.2
27.4
36.1
32.7
33.3
30.4
34.8
41.1
43.6
34.7
39.9
40.2
38.3
15.4
36.9
35.0
36.1
dead
dead
49.8
30.5
31.9
33.4
8ETIC
<% rbc)
1.3
0.1
0.8
1.1
0.3
2.7
1.0
2.2
1.7
o.a
1.0
0.7
1.5
' 1.3
0.4
0.8
0.6
0.1
0.9
1.1
1.8
1.1
2.5
0.8
1.0
1.0
1,3
0.7
0.4
2.4
dead
dead
1.0
1.4
1.9
1.3
                                               D-?:

-------
             SUBCHRONIC TOXICITY OF ORTHO-CRESOl  IN  SPRAGUE DAULEY RATS
                          FEMALE HEMATQLOGY VALUES  (% WBC)
                                [Terminal  Sacrifice]
ANIMAL NO.
                 WBC
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
                            (x
                                             SEGS     BANDS     LYMPHS
                                           (% WBC)   {% WBC)   (% WBC)
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
, 3094
• 3095
3096
3097
3098
3128
3129
3130
3135
3136
3139
9.8
11.7
10.9
5.8
9.6
13.7
11.9
10.8
8.2
12.3
8.3
7.1
13.7
14.1
9,0
7.3
10.2
9.6
8.5
8.4
9.9
7.8
10.8
8.0
10,1
7.8
6.9
6.9
10.0
10,4
dead
dead
11.5
10.1
10.4
11.7
6
31
24
11
17
39
10
1C
20
7
16
16
13
19
14
13
15
13
13
11
19
11
10
24
11
18
10
22
14
20
dead
dead
5
8
39
27
0
2
2
0
0
0
0
1
1
0
1
3
0
1
0
0
0
0
5
1
0
0
0
0
2
C
2
0
2
0
dead
dead
0
0
0
0
88
62
70
87
77
58
87
89
76
90
79
76
85
79
85
86
85
84
79
82
80
52
90
72
85
80
83
72
81
76
dead
dead
94
92
60
73
6
4
3
2
6
3
3
0
1
2
3
1
2
1
0
0
0
2
2
6
1
6
0
3
1
1
3
5
2
3
dead
dead
1
0
1
0
0
1
1
0
0
0
0
0
2
1
1
4
0
0
0
1
0
1
1
0
0
1
0
1
1
1
2
1
1
1
dead
1 dead
0
0
0
0
                                               L>73

-------
                            SUBCHRONIC TOXKITY OF ORTHO-CRESCL IN SPRAGUE OAWIEY RATS
                                             FEMALE WEMATOLOGY VALUES
                                               [Terminal Sacrifice]
                ANIMAL MO,
                                 U3C
                                                SEGS
                                                              SANDS
                                                                             LYMPHS
                                                                                             HONO
                                                                                                            EOS
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 rag/kg/day
(x
(x
                                                                                        C*
                                                                                                       (x
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3039
3090
3091
3092
3093
3094
3095
3096
3097
3098
3128
3129
3130
3135
3136
3139
9.8
11.7
10.9
5.8
9.6
13.7
11.9
10.8
B.2
12.3
8.3
7,1
13.7
H.I
9.0 •
7.3
10.2
9.6
8,5
8.4
9.9
7.8
10.8
8.0
10.1
7.8
6.9
6.9
10.0
10.4
dead
dead
11.5
10.1
10.4
11.7
0.6
3.6
2.6
0.6
1.6
5.3
1.2
1.1
1.6
0.9
1.3
1.1
1.8-
2.7
1.3
0.9
1.5
1.2
1.1
0.9
1.9
0.9
1.1
1.9
1,1
1.4
0.7
1.5
1.4
2.1
cead
dead
0.6
0.8
4.1
3.2
0.0
0.2
0.2
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.1
0.2
0.0
0.1
0.0
0.0
0.0
0,0
0.4
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.1
0.0
0.2
0.0
dead
cead
0.0
0.0
0.0
0.0
3.6
7.3
7.6
5.0
7.4
7.9
10.4
9.6
6.2
11.1
6.6
5.4
11.6
11.1
7.7
6.3
8,7
8.1
6.7
6.9
7,9
6.4
9.7 •
5.8
8,6
6.2
5.7
5.0
8.1
7.9
dead
dead
10.8
9.3
6.2
8.5
0.6
0.5
0.3
0.1
0.6
0.4
0.4
0.0
0.1
0.2
0.2
0.1
0.3
0.1
0.0
0.0
0.0
0.2
0.2
0.5
0.1
0.5
0.0
0.2
0.1
0.1
0.2
0.3
0.2
0.3
•dead
dead
0.1
0.0
0.1
0.0
0.0
0.1
0.1
0.0
0.0
0.0
o.o
0.0
0.2
0.1
0.1
0.3
0.0
0.0
0.0
0.1-
O.D
0.1
0.1
0.0
0,0
0,1
0.0
0.1
0.1
0.1
0,1
0.1
0.1
0.1
dead
dead
0.0
0.0
0.0
0.0
                                                 L>74

-------
                     SUBCBRONtC TOXIC1TY OF  ORTHO-CRESOL  IN SPRAGUE DAWIEY RATS
                                   MALE CLINICAL  CHEMISTRY VALUES
                                         [Interim Sacri fice]
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.

2881
2882
2883
2884
2885
2886
2337
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
29S4
, 2985
2986
2987
2988
2989
GLU
(mg/dl)
132.0
188.9
202.6
211.7
137.0
188.5
184.0
127.6
179.0
102.9
167.3
141.1
144.1
211.3
149.0
149,8
226.3
154,1
285.0
200.9
310.0
213.4
176.7
238.3
157.8
198.8
179.2
279.4
226.3
177.9
215.3
160,0
373.2
112.8
dead
193.9
214.8
212.0
217.8
189.1
BUN
(mg/dl)
11.0
14.2
18.7
7.9
11.1
13.9
12.6
9.1
13.8
12.4
12.6
15.1
12.8
15.6
9.7
11.3
12.4
13.2
17.9
17.3
14.9
15.4
16.6
12,3
16,4
18,8
17.5
11.9
16.1
17.0
16.1
18.5
13,2
16.4
dead
13.8
9.7
19.1
15.3
16.5
• SGPT
(lu/l)
31
40
42
25
27
41
28
37
35
40
37
32
42
41
33
25
23
28
34
40
47
31
30
32
29
46
40
45
43
37
33
27
67
34
dead
38
35
62
24
86
SGOT
Uu/l)
77
87
66
66
82
70
69
87
78
86
67
82
68
76
82
56
67
66
80
80
72
73
77
72
66
81
76
66
70
81
82
75
98
75
dead
73
79
65
68
94
T PRO
Cg/dl>
6.9
6,8
6.4
6.6
6.7
6,7
7.7
7.0
6.3
5.8
6.8
6.7
6.7
5.9
6.5
6.5
6.3
6.8
6.6
6.0
6.1
7.1
6.6
6.9
7,0
6.8
6.5
6.8
6.3
6.1
6.7
6.3
7.0
6.3
dead
6.4
, 6.7
5.9
7.0
6.5
ALB
(g/dt>
4,0
4.2
3.8
3.6
3.7
3.7
4.1
4.0
3.8
3.5
3.8
3.8
3.5
3.4
3.8
3.7
3.8
3.7
3.9
3.3
3.7
3.9
4.0
4.0
4.0
3.8
3.8
3.8
3.5
3,5
4.0
3.6
4.0
3.7
dead
3.7
3.9
3.7
3.9
3.9
GLOB
(9/dl)
2,9
2,6
2.6
3.0
3.0
3.0
3.6
3.0
2.5
2,3
3.0
2.9
3.2
2.5
2.7
2.8
2,5
3.1
2.7
2.7
2.4
3.2
2.6
2.9
3.0
3.0
2.7
3.0
2.8
2,6
2.7
2.7
3.0
2.6
dead
2.7
2.8
2.2
3,1
2.6
ALB/GIQ8
(ratio)
1,379
1,615
1.462
1,200
1.233
1.233
1.139
1.333
1.520
1.522
1.267
1.310
1.P94
1.360
1.407
1.321
1.520
1.194
1.444
1.222
1.542
1.219
1.536
1.379
1.333
1.267
1.407
1.267
1.250 •
1.346
1.481
1.333
1.333
1.423
dead
1,370
1.393
1.682
1.258
1.500
DKOL
(mg/dl)
63.1
50,6
72.4
85.3
S3.0
83.6
84.6
63,7
63.6
50.4
69.2
52.6
66.4
58.5
70.1
73.9
55,2
89.3
56.4
61.7
47.9
83.3
40. 0
68.9
44.7
65.8
65.2
62.7
42,1
68.5
83.3
56.4
61.7
89.3
dead
58.4
77.5
66.9
87.2
57.6
                                                D-75

-------
                             SUaCHROMIC TOXSC1TY OF ORTHC-CRESOL IN SPfUGUE  DAWLEY RATS
                                          MALE CLINICAL CHEMISTRY VALUES
                                                [Interim Sacrifice]
  DOSS LEVEL
  0 mg/kg/day
 50  mg/kg/day
 175  mg/kg/day
.600  mg/kg/day
ANIMAL NO.

2881
2882
2883
28S4
2885
2886
2837
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922 '
2923
2947
2943
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
D 8IL
Cmg/dl)
0.00
0.02
0.03
0,02
0.02
0.03
0.00
0.01
0.04
0.01
0,03
C.04
0.01
0.03
0.02
0.01
0.02
0.02
0.01
0.01
0.02
0.02
0.02
0.01
0.01
0.04
0.03
0.02
0.01
0.00
0,02 .
0.01
0.02
0.02
dead
0.03
0.03
0,02
0.01
0.01
T 311
Cmg/dl)
0.18
0.24
0.16
0.16
0.14
0.16
0.11
0.13
0.17
0.10
0.14
0.20
0.14
0.22
0,22
0.15
0.12
0.16
0.10
0.14
0.08
0.11
0.17
0.16
0.15
0.22
0.21
0.13
0.09
0.13
0.19
0.09
0.13
0.17
dead
0.13
0.20
0.17
0.15
0.20
Ca
Cmg/dl >
12.0
13.1
14.2
12.4
10.3
14.4
11.9
11.5
13.6
11.1
11.0 '
11.6
12.3
13.4
11.4
11.5
13.8
11.4
14.8
14.8
13.3
11.9
10.7 -
12.5
10.5
14.2
14.2
14.4
15.0
14.0
11.3
12.0
14.8
11.3
dead
12,8
12.3
12.9
11.6
12.4
Ha
(Heq/L)
143
139
157
145
144
141
144
146
145
141
141
146
139
146
141
142
142
144
158
152
154
185
142
143
141
160
142
143
143
164
143
144
150
144
dead
158
145
153
144
133
K
(Meq/D
7.0
6.9
10.7
6.8
6.2
9.3
6.9
8.7
8.5
7.6
7.1
11.2
6.1
8.3
6,1
7.1
5.9
7.6
9.5
8,0
8.1
5.3
6.7
6.8
6.6
7.8
6,7
5.8
7.4
10.9
7.1
10.5
12.3
6.7
dead
6.6
6.5
8.6
5.5
7.6
Ct
(Heq/U
98
94
110
103
101
98
101
101
101
101
99
102
96
102
97
100
98
102
111
107
108
102
98
100
98
114 •
94
97
96
118
99
104
104
102
dead
112
99
108
98
89
AU PHCS
CIu/l)
94
145
225
106
110
182
98
113
233
106
73
90
92
276
51
64
161
71
260
127
250
56
70
61
102
259
239
123
155
201
87
60
96
79
dead
146
64
171
83
306
C02
(Meq/l)
25
29
21
29
28
21
25
29
24
25
29
25
27
18
27
27
23
21
25
22
19
31
30
25
29
26
22
25
ia
23
25
24
11
27
dead
24
28
23
27
23
GREAT

0.83
0.80
0.62
0.69
0.74
0.63
0.75
0.72
0.66
0.70
0,69
0.88
0.82
0,64
0.82
0.67
0.67
0.64
0.73
0.80
0.62
0.80
0.73
0.76
0.77
C.69
0.70
0.62
0.70
0.58
0.86
0.66
0.68
0.74
dead
0.65 .
-0.76
0.71
0.71
0.66
PHCS
Lrcs/di
10'. 4
9.5
11.5
11.3
10.5
11,1
11.3
10.6
11.4
10.2
9.5
11.7
9,4
9.2
9.5
8.3
9.8
13.3
11.7
11.1
10.8
9.7
10.1
11.0
9.9
1Z.1
10.1
10.8
9.8
12.2
10.3
13.0
12.4
10,1
dead
9.8
10.3
11.5
9.0
9.7
                                                D-76

-------
                     SU8CHRQNIC TOXICITY  OF ORTHO-CRESOL  IN SPRAGUE DAWliY RATS
                                   MALI CLINICAL CHEHISTRY VALUES
                                        [Terminal Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
AH [HAL NO.

2S91
2892
2393
2894
2895
2896
2897
2898
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2994
2996
2998
2999
3001
3003
3005
3007
. GLU
(mg/dl)
365.2
225.9
195.7
242.7
196.0
228.2
212.0
268.5
154.2
279.8
314,1
196.0
173.1
222.1
261.6
341,2
190.3
198.9
167.5
197.4
292.2
240.9
242. 7
272.3
205.8
215.5
260.4
277.1
197.6
278.2
157.1
244.6
151.9
156.1
209.6
201.1
125.0
170.9
260.5
197.8
BUN
(mg/dl 5
18.2
15.4
15.5
14.1
11.9
13.5
15.9
10.6
14.0
13.8
11.8
16.7
11.4
10.8
16.7
14.8
9.4
10.4
12.8
11.6
10.1
13.5
15.3 .
14.9
17. 0_
12.3
15.3
13.9
11.6
14.1
14.1
19.2
11.4
14.0
13.1
11.5
12.3
17.3
15.8
12.5
SGPT
Clu/l)
26
70
29
29
34
25
39
28
489
30
22
28
37
30
111
30
25
29
17
23
23
81
60
32
34
23
28
16
30
65
35
24
27
597
31
36
33
27
20
46
SCOT
Uu/l)
86
97
68
60
77
69
91
83
587
82
49
86
92
52
240
76
62
75
60
63
72
140
93
79
94
60
76
55
85
101
86
64
55
716
75
73
76
86
54
85
T PRO
(S/dl)
7.4
6.2
7.0
6.4
6.7
6.7
6.8
5.2
7.2
7.4
7.2
6.6
5.9
6.6
7.1
7.7
5.1
5.3
5.4
4.9
6.9
7.0
6.1
6.3
6.5
6.9
7.0
6.4
7.5
6.8
6.8
6.0
6.3
7.9
6.1
5.3
6.Z
6.4
5.7
6.5
ALB
(g/di)
4.1
3.5
3.8
3.5
3.8
3.7
3.8
3.1
4.0
3.9
4.0
3.6
3.9
3.5
3.8
4.0
3.2
4.0
4.1
3.5
3.9
4.1
3.5
3.4
3.5
3.8
3.8
3.5
3.8
4.0
3.5
3.2
3.5
4.1
3.5
3.3
3.6
3.9
3.6
3.7
GLOB
(g/dl)
3.3
2.7
3.2
2.9
2.9
3,0
3.0
2.1
3.2
3.5
3.2
3.0
2.0
3.1
3.3
3.7
1.9
1.3
1.3
1.4
3,0
2.9
2.6
2.9
3.0
3.1
3.2
2.9
3.7
2.8
3.3
2.8
2.8
3,8
2.6
2.0
2.6
2.5
2.1
2.8
ALB/GLOB
(ratio)
1.242
1.296
1.188
1.207
1.310
1.233
1.267
1.476
1.250'
1.114
1.250
1.200
1.950
1.129
1.152
1.081
1.684
3.077
3.154
2.500
1.300
1.414
1.346
1.172
1.167
1.226
1.188
1.207
1.027
1.429
1.061
1.143
1.250
1.079
1.346
1.650
1.385
1.560
1.714
1.321
CHOL
(mg/dl)
81.5
42.8
78.8
94.3
138. 7
84.9
85.1
77.9
66.0
76.9
52.5
91.2
56.9
90.0
50.2
97.6
75.2
67.9
63.9
62.8
61.2
95.8
54.0
69.4
81.0
69.0
69.4
53.0
63.5
76.1
73.1
121.5
60.3
128.2
69.1
101.7
79.8
92.1
57,0
47.4
                                               D-77

-------
                        SU8CHMNIC TOX1C1TY OF ORTHO-CRESOL IN SPRAGUE DAULEY  RATS
                                    HALE CLINICAL CHEMISTRY VALUES
                                         [Terminal Sacrifice]
DOSE LEVEL
AN1MAI/NQ.   D BIU   T Bit     Ca      Na      K       Cl    ALK PHOS    C03     CREAT    PHOS
           (mg/dl)   (mg/dl)  {mg/dl>     
-------
                     SUBCHRONIC TOXIC1TY OF ORTHO-CRESOL  IN  SPRAGUE DAWLEY RATS
                                 FEMALE CLINICAL CHEMISTRY  VALUES
                                        [Interim Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
                ANIMAL-NO.    GLU      BUN     SGPT     SCOT    T PRO    ALB'   GLOB   ALB/GLOB    CHOL
                            Cmg/dU  (mg/dl)  (Iu/l)   (Iu/l)   
-------
                           SUBCHRGNIC TOXICITY OF  ORTHQ-CRESQL IN SPRAGUE DAULEY RATS
                                        FEMALE CLINICAL CHEMISTRY VALUES
                                               [Interim Sacrifice]
 DOSE LEVEL
 0 mg/kg/day
SO mg/kg/day
175 mg/kg/day
600 mg/kg/day
AN I HAL NO.

3013
30H
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
0 B1L
Cmg/dl)
0.02
0.00 .
0.01
0,01
0.01
0.02
0.04
0.01
0.01
0.02
0.07
0.01
0.03
0.03
0.02
0.01
0.02
0.02
0.00
0.02
0.02
0.01
0.08
0.02
0.02
0.00
0.01
0.01
0.02
0.04
dead
dead
0.00
0,04
0.00
0.01
0.01
0.01
0.01
dead
T BIL
(mg/dl)
0.17
0.13
0.15
0.11
0.11
0.11
0.20
0.07
0.22
0.14
0.21
0.14
0.20
0.18
0.12
0.14
0.10
0.19
0.10
0.12
0.15
0.13
0.17
0.18
0.15
0.22
0.08
0.14
0.15
0.17
dead
dead
0.15
0.24
0.17
0.17
0.21
0.16
0.13
dead
Ca
Crog/dl3
14.0
15.2
12.4
15.0
12.0
14.8
,13.6
14.0
15.1
U.O
12.5
12.8
17.0
11.9
12.8
13.3
12.2
10.8
11.7
13.3
13.7
11.7
13.5
12.6
13.0
12.3
12.3
15.2
12.7
14.3
dead
dead
12.4
13.1
14.8
11.8
13.2
12.9
15.4
dead
Na
(Meq/l)
145
139
146
145
143
155
141
141
154
164
150
157
147
140
143
162
146
188
145
150
142
191
144
144
183
142
142
145
176
147
dead
dead
144
151
141
141
1*3
143
145
dead
<
(Meq/O
7.5
7.8
10.4
7.8
6.4
10.0
9.1
9.1
7.6
13.4
8.5
7.7
9.4
7.8
6.9
8.4
7.7
10.9
8.1
8.3
8.3
9.9
8.0
8.0
10.1
7.0
7.8
10.1
9.1
7.9
dead
dead
9.5
9.7
7.7
7.0
9.5
9.0
6.9
dead
Cl
(Meq/l)
ICO
97
107
100
100
110
99
98
111
123
102
108
101
99
100
117
101
145
103
103
97
148
100
100
136
100
101
103
129
104
dead
dead
100
109
99
95
101
101
99
dead
ALK ?HOS
ciu/n
97
90
127
85
72
59
143
120
60
76
87
88
364
141
88
108
38
50
58
88
66
116
216
96
46
43
110
89
98
159
dead
dead
82
117
134
46
122 '
92
65
dead
C02
(Meq/l)
20
21
20
29
26
19
20
20
22
20
24
19
20
20
25
21
22
26
26
23
23
24
19
19
24
24
23
12
18
22
dead
dead
20
18
19
28
21
20
17
dead
GREAT
(mg/dl)
0.67
0.62
0.80
0.62
0.71
0.72
0.62
0.59
0.66
0.66
0.75
0.72
0.67
0.77
0.72
0.52
0.73
0.67
0.69
0.65
0.69
0.72
0.75
0.56
0.68
0.89
0.77
0.66
0.72
0.76
dead
dead
0.86
0.69
0.67
0.83
0.70
0.86
0.66
dead
PHOS
(mg/d'l)
9.6
9.9
10.9
10.6
8.1
10.8
10.2
10.9
9.9
11.0
9.4
9.6
11.9
9.4
' 8.5
10.3
8.5
8.8
8.2
11.0
9.7
9.3
10.1
9.4
10.1
9.6
9.2
12.0
9.7
10.6
dead
dead
10.1
10,4
10.0
9.1
9.2
9.6
8.8
dead
                                                     D-80

-------
                     SU8CH8QN1C TOXIC ITY OF ORTHO-CRESOL  IN  SPRAGUE DAWLEY RATS
                                  FEHALE CLINICAL  CHEMISTRY  VALUES
                                        [Terminal  Sacrifice!
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
AMIMAL MO.

3023
3024
3025
3026
3027
3023
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3130
3135
3136
3139
GLU
(mg/dl)
137.7
151.5
155.4
160.6
198.2
202.1
298.8
162.2
147.7
156.3
206.0
163.2
204.5
158.0
142.7
288.7
202.3
219.6
128.1
140.1
186.8
182.3
162.4
264.2
204.9
169.0
106.4
210.4
243.4
205.0
168.2
124.6
148.8
158.7
SUN
(mg/dt)
13.0
16.0
15.0
14.3
16.2
16.0
13.7
13.5
12.6
15.8
14.4
10.7
14.7
9.1
20.3
11.6
15.1
12.5
12.8
10.6
19.5
13.2
19.7
13.7
18.0
11.2
19.7 '
14.2
14.0
14.3
20.4
15.5
15.0
14.6
SGPT
(lu/U
27
18
27
22
31
22
25
18
26
26
21
17
74
31
28
36
44
25
25
21
21
28
28
43
B5
27
32
80
25
27
46
24
27
23
SGOT
Uu/l)
77
65
82
55
103
55
81
81
83
68
85
- 71
'153
74
65
97
101
71
81
66
46
89
65
85
150
93
82
176
69
77
89
65
121
56
T ?m
(g/du
7.2
6.3
6.8
6.7
7.1
7.5
a.3
6.2
5.1
6.3
7.6
5.3
6.6
6.1
6.8
8.0
7.8
7.2
6.2
6.4
7.2
7.1
7.6
8.9
7.2
7.5
6.4
8.1
6.8
7.3
7.2
6.2
7.6
6.2
ALB
(g/dl)
4,5
4.0
4.0
4.4
"4.1
4.7
4.7
3.8
4.1
3.7
4,5
4.6
4.2
3.9
3.9
4.6
4.5
4.7
4.5
4.2
4.1
4.4
4.6
5.3
4.6
4.3
3.9
4.5
3.9
4.4
4.6
4.0
4.2
3.7
GLOB
Ca/di)
2.7
2.3
2.8
2.3
3.0
2.8
3.6
2.4
1.0
2.6
3.1
0.7
2.4
2.2
2.9
3.4
3.3
2.5
1.7
2.2
3.1
2.7
3.0
3.6
2.6
3.2
2.5
3.6
2.9
2.9
2.6
2.2
3.4
2.5
ALB/GLOB
(ratio)
1.667
1.739
1.429
1.913
1.367
1.679
1.306
1.583
4,100
1.423
1.452
6.571
1.750
1.773
1.345
1.353
1,364
1.SSO
2.647
1.909
1.323
1.630
1.533
1.472
1.769
1.344
1.560
1.250
1.345
1.517
1.769
1.818
1,235
1.480
CHOL
(mg/dl)
70.4
71.9
94.8
106.4
63.9
123.6
63.3
112.7
100.8
89.5
88.5
74.9
121,1
72.4
86.3
105.3
38.6
48.7
80.9
69.0
62.9
103.3
B6.8
119.8
129.0
118.7
65.4
129.8
61.2
86. 3
89.8
90.3
121,4
95.0
                                             D-81

-------
                       SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWUEY RATS
                                  FEMALE CLINICAL CHiMISTRY VALUES
                                       {Terminal Sacrifice]
ANIMAL 'NO.
DOSE LEVEL
0 mg/kg/day 3023
3024
3025
3026
3027
302S
3029
3030
3031
3032
50 ing/kg/day 3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
175 mg/kg/day 3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
600 mg/kg/day 3130
3135
3136
. . 3139 .
D B!L
(mg/dl)
0.00
0.00
0.02
0.00
0.02
0.01
0.02
0.01
0.00
0.02
0.02
0.00
0.02
o.do
0.01
0.02
0.01
0.01
0.00
0.00
0.02
0.01
0.02
0,03
0.02
0.02
0.01
0.02
0.01
0.00
0.02
0.01
O.QO
0.02
T BIL
(mg/dl)
0.19
0.04
0.09
0.10
0.09
0.08
0.06
0.06
0.09
0.06
0.05
0.13
0.09
0.06
0.10
0.05
0.08
0.1V
0.11
0.08
0.01
0.09
0.06
0.10
0.08
0.07
0.12
0.21
0.02
0.12
0.13
0.10
0.04
0.08
CA
(mg/dl)
12.7
12.8
13.9
13.6
13.8
14.1
13.5
12.1
12.3
11.0
13.3
13.7
12.2
12.6
11.8
13.8
12.7
14.8
13.5
13.2
12.8
12.3
14.8
16.0
13.7
13.4
11.5
13.7
11.0
13.1
13.7
12.3
13.0
10.8
Na
(Meq/l)
149
150
153
153
151
154
156
153
146
151
147
154
155
153
152
155
159
148
157
157
159
149
151
158
148
152
150
224
55
149
CHS
153
155
160
K
CMeq/l)
9.5
10.1
11.3
9.6
8.7
8.1
8.4
8.7
9.6
10.3
9.8
8.2
10.6
11.1
12.3
10.1
9.5
a. s
13.2
8.2
8.2
7.6
9.6
15.8
8.9
9.9
11.0
16.5
8.8
10,3
CHS
10.8
10.7
10.5
Ct
(Meq/l)
101
103
101
102
104
100
92
105
104
104
103
95
102
97
101
98
99
104
99
108
96
102
104
95
103
101
106
146
92
101
QMS
104
102
97
ALK PKOS
(lu/l)
30
41
70
51
38
61
55
41
38
58'
30
36
100
30
58
56
24
25
75
61
31
84
49
30
34
42
71
48
50
149
58
34
34
48
C02
(Heq/l)
20
16
24'
21
25
23
18
27
20
24
23
19
25
17
17
22
26
18
13
20
, 22
17
26
19
25
20
19
22
18
23
QMS
25
22
25
GREAT
Crag/dl)
0.95
0.74
0.76
0.73
0.91
0.65
0.74
0.60
- 0.71
0.65
0.75
0.69
0.68
0.64
0.73
0.81
0.77
0.84
0.78
0.65
0.66
0.86
0.76
0.75
0.71
0.74
0.71
0.96
0.74
0.97
0.77
0.66
0.76
0.65
PHOS
(mg/dt.
8.1
9.0
9.3
8.1
10.3
9.5
8.5
12.4
7.1
10.9
9.5
7.0
10.6
7.6
10.7
8.S
9.1
7,6
8.0
7.6
7.5
7.6
10.3
12.1
10,5
10,0
9.6
7.3
8.4
9.5
12.4
12.0
10.6
9.4
QNS = quantity not  sufficient  to  assay.
                                             D-82

-------
     SUBCHROMIC TQXICITY OF OSTHO-CRESOL  IN  SPRAGU'E DAULEY RATS
      RELATIVE HALE ORGAN WEIGHT  DATA (X  Terminal  Body Height)
                        [Terminal Sacrifice]
                ANIMAL NO.   HEART  LIVER   SPLEEN  KIDNEY-LFT  KIDNEY-RT
 DOSE LEVEL
 0 mg/kg/day
50 rag/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
0.360
0.292
0.335
0.302
0.319
0.334
0.329
0,299
0.366
0.317
0.317
0.300
0.330
0.323
0.297
0.296
0.299
0.312
0.307
0.326
0.350
0.336
0.285
0.314
0.692
0.257
0.368
0.347
0.273
0.363
0.31H
0.313
0.304
0.296
0.306
0.363
0.292
0.264
0.317
0.293
3.520
3.281
3.499
3.099
3.515
3.292
3.313'
3.185
3.158
3.762
3.132
3.256
3.195
3.021
3.038
3.772
3.446
2.983
3.661
3.605
2.837
3.533
3.283
3.244
7.044
2.986
2.877
3.705
3.006
3.890
3.372
3.701
3.278
2.875
3.027
3.032
3.374
2.755
3.389
3.791
0.150
0.143
0.134
0.131
0.111
0.137
0.146
0.138
0.142
0.151
0.153
0.120
0.153
0.136
0.129
0.157
0.143
0.135
0.193
0.129
0.147
0.138
0.132
0.117
0.312
0.112
0.117
0.160
0.131
0.161
0.183
0.145
0.149
0.159
0.123
0.142
0.135
0.133
0.135
0.161
0.375
0.390
0.385
0.349
0.358
0.349
0.339
0.341
0.367
0.429
0.378
0.341
0.343
0.296
0.332
0.431
0.370
0.317
0.392
0.417
0.327
0.405
0.390
0.388
0.841
0.369
0,360
0.381
0.375
0.368
0.357
0.357
0.409
0.315
0.366
0.360
0.356
0.280
0.333
0.330
0.374
0.397
0.379
0.345
0.373
0,372
0.336
0.343
0.375
0.455
0.379
0.326
0,356
0,305
0.355
0.398
0.380
0.335
0.401
0.414
0.329
0.425
0.398
0.408
0.868
0.330
0.393
0.400
0.359
0.367
0.369
0.343
0.437
0.292
0.397
0.383
0.370
0.305
0.381
0.343
                                      D-83

-------
         SUBCHRONIC TOXICITY OF ORTHO-CRESOL  IN  SPRAGUE DAWL£Y RATS
          RELATIVE MALE CRGAM WEIGHT  DATA  <%  Terminal Body yeight)
                            [Terminal  Sacrifice]
                ANIMAL NO.   TEST1S-LFT   TESTIS-RT  ADRENALS  BRAIK  THY./PARA.
 DOSE LIVEL
 0 mg/kg/day
50 mg/kg/day
2391
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
0.343
0.361
0.339
0.352
0.308
0.320
0.326
0.338
0.342
0.285
0.296
0.234
0.365
0.285
0.295
0.211
0.295
0.309
0.328
0.308
0.358
0.311
0.257
0.352
0.754
0.315
0.124
0.329
0.285
0.253
0.348
0.181
0.331
0.253
0.360
0.35S
0.297
0.282
0,359
0.249
0.350
0.365
0.352
0.337
0.308
0.304
0.315
0.343
0.343
0.284
0.296
0.248
0.353
0.300
0.309
0.315
0.297
0.289
0.328
0.310
0.353
0.314
0.269
0.336
0.783
0.327
0.124
0.331
0.286
0.268
0.348
0.302
0.336
0.244
0.350
0.363
0.294
0.278
0.370
0.220
0.012
0.012
0.010
0.010
0.009
0.010
0.012
0.012
0.012
0.007
0.013
0.010
0.010
O.D10
0.010
0.005
0.009
0.007
0.013
0.009
0.010
0.012
0.011
0.011
0.024
0.012
0.010
0.006
0.010
0.009
0.012
0.010
0.010
0.009
0.008
0.013
0.011
0.007
0.009
0.010
0.419
0.479
0.398
0.438
0,400
0.377
0.375
0.415
0,405
0.360
0.417
0.394
0.408
0.418
0.416
0.410
0.381
0.366
0.420
0.414
0.416
0.399
0.413
0.454
0.815
0.399
0.451
0.384
0.366
0.398
0.446
0.370
0.357
0.380
0.428
0.467
0.371
0.373
0.409
0.357
0.005
0.005
0.007
0.006
0.007
0.004
o:oos
0.005
0.004
0.009
0.005
0.009
0.005
0.008
0.004
0.004
0.006
0.004
0.007
0.004
0.007
0.004
0.008
0.005
0.015
0.009
0.004
0.006
0.005
0.005
0.006
0.004
0.005
0.005
0.006
'0.007
0.002
0.005
0.009
0.003
                                      D-84

-------
     SUBCHRONIC TOXJC1TY OF ORTHO-CR1SOL  IN  SPRAGUE DAWLEY SATS
      RELATIVE HALE ORGAN WEIGHT DATA (%  Terminal Sody Weight)
                        [Terminal Sacrifice]
                ANIMAL TO.  HEART  LIVER   SPLEEN   KIDNEY-LFT
 COSE i;EVEL
175 ms/kg/day
600 mg/kg/day
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2963
2969
2970
2971
2972
2973
2974
2975
2976
2990
2991
2994
2996
2998
2999
3001
3002
3003
3005
3007
3009
0.320
0.265
0.366
0.279
0.320
0.325
0.311
0.334
0.347
0.319
0.362
0.333
0.296
0.289
0.324
0.327
0.304
0.293
0.271
0.319
0.313
0.331
0.321
0.322
0.3&6
0.324
0.319
0.330
0.300
0.355
0.307
0.306
3.386
3.145
3.172
3,239
3.533
3.218
3.792
3.378
3.612
3.440
3.219
3.282
3.281
3.360
3.260
3.256
2.907
2.921
2.917
3.981
3.300
3.796
3.904
3.657
3.438
3.189
3.091
3.557
3.086
3.931
3.911
3.427
0.130
0.135
0.131
0.126
0.116
0.141
0.130
0.137
0.157
0.139
0.168
0.144
0.151
0.142
0.146
0.139
0.117
0.155
0.149
0.115
0.120
0.151
0.135
0.148
0.142
0.136
0.148
0.122
0.160
0.147
0.132
0.131
0.366
0.327
0.373
0.373
0.410
0.436
0.454
0.447
0.379
0.378
0.404
0.360
0.356
0.375
0.446
0.388
0.315
0.362
0.360
0.375
0.401
0.430
0.475
0.407
0.464
0.415
0.399
0.412
0.350
0.474
0.403
0.445
0.339
0.341
0.394
0,360
0.385
• 0.386
0.450
0.411
0.400
0.383
0.378
0.380
0.366
0.330
0.465
0.401
0.310
0.373
0.335
0.411
0.377
0.438
0.473
0.418
0.474
0.414
0.429
0.422
0.359
0.490
0.403
0.450
                                         D-85

-------
         SUBCHRQNIC TOXICITY OF ORTHO-CRESQL IN SPRAGUE  DAWLEY SATS
          RELATIVE MALE OR5AW UEEGHT DATA (% Terminal  Body Weight)
                            [Terminal Sacrifice]
                ANIMAL NO.  TEST1S-LFT  TESTSS-RT   ADRENALS   8RAIN   THY./PARA.
 DCSE LEVEL
175 mg/'
-------
     SUiCHRONIC TOXiCITY OF  OSTHO-CRESQL  IN SPRAGU6 DAULEY RATS
     RELATIVE FEMALE ORGAN UEIGHT DATA  (% Terminal Body Weight)
                        [Terminal Sacrifice]
                ANIMAL NO.   HEA8-T   LIVES  SPLEEN  KIDMEY-LFT  KIDNEY-RT
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
0.351
0.308
0.324
0.368
0.417
0.341
0.330
0.330
0.346
0.316
0.448
0.347
0.407
0.366
0.364
0.297
0.373
0.361
0.324
0.322
0.400
0.346
0.372
0.360
0.330
0.36S
0.337
0.323
0.380
0.321
0.546
0.341
0.392
0.352
0.329
0.365
0.361
0.350
0.400
0.374
'3.081
2.665
3. 158
3.382
3.349
3.154
3.500
3.409
3.135
2.982
3 .477
3.519
3.011
3.079
3.258
2.745
3,135
3.481
3.346
3.243
3.116
3.064
3.519
3.057
2.801
3.071
2.9S2
3.233
3,416
3.037
3.225
3.030
3.165
3.269
3.225.
2.735
3.092
3.399
3.425
3.106
0.193
0.173
0.175
0.219
0.190
0.183
0.192
0.224
0.195
0.182
0.177
0.217
0.210
0.198
0.139
0.169
0.188
0.187
0.159
0.188
0.156
0.175
0.185
0.170
0.148
0.192
0.159
0.194
0.171
0.153
0.199
0.165
0.184
0.196
0.169
0.183
0.219
0.179
0.207
0.160
0.4CS
0.302
0.309
0.375
0.441
0.369
0.397
0.419
0.366
. 0.338
0.435
0.380
0.443
0.396
0.361
0.338
0.482
0.374
0.372
0.368
0.344
0.391
0.407
0.370
0.347
0.400
0.334
0.419
0.431
0.402
0.427
0.365
0.398
0.380
0.392
0.335
0.374
0.395
0.398
0.340
0.458
0.301
0.304
0.415
0.439
0.366
0.407
0.439
0.389
0.349
0.464
0.395
0.384
0.381
0.399
0.394
0.528
0.361
0.376
0.368
0.353
0.445
0,438
0.354
0.363
0.433
0.359
0.447
0.438
0.378
0.421
0.359
0.409
0.407
0.362
0.345
0.373
0.429
0.421
0.356
                                       r>87

-------
            SUBCHRQNiC TOX1C1TY OF ORTHQ-CRESOL !M SPRAGUE  DAytEY RATS
            RELATIVE FEMALE ORGAN WEIGHT DATA {% Terminal Body Weight)
                             [Terminal Sacrifice]
                   ANIMAL  NO.  OVARY-LFT  OVARY-HT  ADRENALS  BRAiM  THY./PARA,
     DOSE 'LEVEL
0 mg/kg/day 3023
3024
3025
3026
3027
3028 ,
3029
3030
3031
3032
3033
3034
3035
3036
3037
. 3038
3039
3040
3041
3042
50 mg/kg/day 30S6
3057
30S8
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
O.D16
0.018
0.015
0.017
0.037
0.011
0.015
0.017
0.014
0.018
0.014
0.018
0.011
0.014
0.013
0.010
0.023
0.018
0.010
0.016
na
0.016
0.014
0.013
0.019
0.023
0.008
0.003
0.014
0.014
0.018
0.012
0.012
0.016
0.013
0.008
0.017
0.019
0.021
0.014
0.017
0.011
0.016
0.020
0.032
0.012
0.017
0.016
0.018
0.011
0.019
0.018
0.012
0.021
0.016
0.009
0.016
0.019
0.006
0.018
na
0.012
0.012
0.013
0.018
0.022
na
0.007
0.016
0.012
0.020
0.014
0.017
0.015
0.007
0.017
0.013
0.018
0,021
0.014
0.030
0.021
0.019
0.023
0.024
0.023
0.024
0.021
0.020
Q.Q25
0.022
0.033
0.019
0.021
0.029
0.022
0.030
0.024
0.020
0.030
0.027
0.026
0.020
0.021
0.032
0.026
0.015
0.022
0.027
0.016
0.023
0.024
0.019
0.025
0.018
0.016
0.023
0.026
0.022
0.014
0.789
0.710
0.679
0.793
0.748
0.699
0.752
0.800
0.738
0.730
0.807
0.815
0.783
0.780
0.766
0.740
0.739
0.812
0.731
0.829
na
0.694
0.659
0.695
0.766
0.668
0.702
0.678
0.349
0,616
0.780
0.629
0.752
0.677
0.631
0.612
0.691
0.828
0.756
0.582
0.014
0.008
0.011
0.010
0.007
0.008
0.010
0.009
0.008
0.005
0.011
0.006
0.007
0.013
0.006
0.012
0.012
0.010
0.011
0.012
0.007
0.008
0.007
0.008
0.006
0.008
0.008
0.012
0.009
0.011
0.010
0.008
0.010
0.010
0.006
0.006
0.008
0.007
0.006
0.009
na  =  no  data  available.
                                           D-88

-------
     SUBCHRON1C TOXICITY OF ORTHO-CSESOL IN SPRAGUE DAUIEY RATS
     RELATIVE FEMALE ORGAN WEIGHT DATA (X Terminal Body Weight)
                        [Terminal Sacrifice]
                ANIMAL SO.  HfART  LIVER  SPIEEN  KIONEY-LFT  KIONET-RT
 DOSS LEVEL
175 mg/kg/day
600 mg/kg/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
310!
3102
3103
3104
3105
3106
3107
3108
3130
3135
3136
3139
0.376
0.400
0.328
0.452
'0.396
0.344
0.340
0.310
0.399
0.342
0.324
0.314
0.346
0.372
0.343
0.335
0.317
0.364
0.403
0.336
0.363
0.308
0.362
0.397
3.184
3.265
3.083
4.023
3.350
3.451
3.414
2.965
3.145
3.285
3.344
3.081
2.854
3.123
3.122
3.363
3.034
2.850
3.290
3.106
3.191
3.293
3.215
3.577
0.223
0.206
0.220
0.160
0.201
0,187
0.188
0,202
0.245
0.216
0.196
0.173
0.232
0.181
0.166
0.177
0.191
0.186
0.169
0.159
0.211
0.207
0.153
0.245
0.391
0.462
0.403
0.474
0.411
0.332
0.415
0,351
0.454
0.334
0.392
0.350
0.307
0.39Q
0.463
0.356
0.329
0.370
0.426
0.388
0.377
0.387
0.363
0.421
0.412
0.471
0.422
0.500
0.432
0.338
0.427
0.374
0.485
0.377
0.397
0.367
0.308
0.613
0.416
0.402
0.332
0.363
0.420
0.398
0.390
0.418
0.385
0.409
                                     D-89

-------
        SUBCHRONIC TOXICITY OF  ORTHO-CRESOL  IN  SPRAGUE DAULEY RATS
        RELATIVE FEMALE ORGAN WEIGHT  DATA  C%.Terminal Body Weight)
                           [Terminal  Sacrifice]
                ANIKAL NO.   OVARY-LFT   OVARY-RT  ADRENALS  ERAJN  IKY./PARA,
 DOSE LEVEL
175 mg/kg/day
600 mg/kg/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
3130
3135
3136
3139
0.013
0.012
0.01S
0.017
0.016
0.018
0.017
0.032
0.013
0.014
0.016
0.015
0.018
0.013
0.016
0.011
0.011
0.011
0.019
0.021
0.026
0.017
0.017
0.016
0.019
0.011
0.01S
0.018
0.016
0.020
0.019
0.028
0.018
0.019
0.018
0.011
0.016
0.021
0.014
0.008
0.013
0.013
0.017
0.014
0.02T
0.009
0.014
0.011
0.023
0.024
0.020
0.025
0.024
0.023
0.025
0.029
0.024
0.026
0.015
0.012
0.024
0.024
0.028
0.014
0.022
0.019
0.034
0.023
0.025
0.029
0.029
0.026
0.769
0.897
0.838
0.709
0.720
0.628
0.762
0.784
0.725
0.793
0.282
0.625
0.662
na
0.835
0.662
0.630
0.776
0.833
0.756
0.820
0.831
0.797
0.754
0.011
0.015
0.011
0.008
0.012
0.008
0.010
0,008
0,012
0.010
0.008
0.008
0.007
0.005
0.012
0.003
0.009
0.012
0.009
0.011
0.013
0.009
0.009
0.012
                                          D-90

-------
      SUiCHRONIC TOXICITY  OF  QRTHQ-CRESOL IN SPRAGUE DAULEY RATS
                      MALE ORGAN WEIGHT DATA 
-------
               SUBCHRON1C TOX1CITY OF ORTHO-CRESOL IN SPRAGUE DAULET RATS
                               MALE  ORGAN WEIGHT DATA (g)
                                  [Terminal  Sacrifice]
                ANIMAL NO.   TESTIS-LFT   TESTIS-RT  ADREKALS  BRAIN  THY./PARA.   TERM.  UGT,
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910 •
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
1.827
1.599
1.720
1.723
1.566
1.752
1.827
1.876
1,656
1.712
1.620
1.272
1.918
1,533
1.560
1.090
1.717
1.706
1.667
1.493
1.902
1.787
1.348
1.707
1.929
1.698
0.563
1.783
1.601
1.364
1.665
1.108
1.995
1.337
1,816
1.806
1.674
1.665
1.980
1.478
1.862
1.618
1.783
1.653
1.570
1.667
1.765
1.906
1.661
1.703
1.624
1.349
1.S57
1.613
1.633
1.624
1.730
1.598
1.668
1.500
1.879
1.804
1.412
1.632
2.0C5
1.761
0.562
.795
.606
.444
.663
.848
2.029
1.290
1.766
1.827
1.658
1.645
2.043
1.305
0/063
0.053
0.051
0.048
0.047
0.054
0.068
0.064
0.059
0.040
0.071
0.053
0.050
0.055
0.051
0.027
0.055
0.041
0.066
0.045
0.055
0.068
0.060
0.054
0.062
0.062
0.044
0.034
0.055
0.048
0.056
0.060
0,061
0.045
0.041
0.067
0.064
0.044
0.049
0.058
2.227
2.124
2.016
2.148
2.038
2.067
2.101
2.301
1.960
2.157
2.285
2.138
2.146
2.246
2.194
2.117
2.222
2.020
2.136
2.006
2.214
2.293
2.164
2.202
2.086
2.148
2.044
2.082
2.055
2.143
2,131
2.267
2.151
2.008
2.159
2.352
2.092
2.206
2.260
2.118
0.027
0.023
0.034
0.028
0.034
0.024
0.026
0.027
0.017
0.052
0.028
0.050
0.026
0.044
0.022
0.022
0.033
0.021
0.036
0.019
0.037
0.025
0.040
0.026
0.038
0.051
0.018
0.031
0.026
0.026
0.031
0.024
0.032
0.024
0,028
0.034
0.014
0.027
0.048
0.020
532
443
507
490
509
548
560
555
484
600
548
543
526
537
528
516
583
552
508
454
532
575
524
485
256
539
453
542
561
539
478
612
603
529
505
504
564
591
552
594
                                             D-92

-------
      SUBCHROH1C TOXICITY OF QRTHQ-CRESOL IN SPRAGUE  DAULEY  RATS
                      MALE ORGAN HEIGHT DATA (g)
                         tTerminal Sacrifice]
                ANIMAL NO.  HEART   LIVER  SPLEEN   KSDNEY-LFT  KIDNEY-RT
 DOSE LEVEL
175 mg/kg/day
600 mg/kg/day
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
299Q
2991
2994
2996
2998
2999
3001
3002
. 3003
3005
3007
3009
1.714
1.591
1.735
1.616
1.748
1.732
1.932
1.761
1.897
1.568
1.902
1.836
1.702
1.795
1.583
2.018
1.837
1.483
1.317
1,533
1.636
1.650
1.797
1.370
1.835
1.377
1.495
1.760
1.532
1.750
1.560
1.373
18.148
18.872
15.227
18.786
19.327
17.150
23.550
17.834
19.719
16.890
16.900
18.115
18.866
20.366
15.908
20.087
17.585
14.807
14.177
19.111
17.257
18.904
21 .863
15.542
17.260
13.554
14.464
18.994
15.740
19.379
19.869
15.388
0.697
0.811
0.627
0.733
0.637
0.751
0.803
0.722
0.859
0.683
0.881
0.795
0.870
0.884
0.711
0.860
0,709
0.785
0.723
0.551
0.628
0.751
0.756
0.627
0,713
0.578
0.691
0.649
0.814
0.725
0.671
0.588
1.962
1.959
1.792
2.162
2.241
2.325
2.818
2.362
2.067
1.858
2,119
1.985
2,047
2.326
2.177
2.391
1.903
1.834
1.749
1.802
2.095
2.140
2.661
1.730
2.327
1.763
1.869
2.202
1.787
2.339
2.049
2.000
1.818
2.047
1.891
2.089
2.105
2.057
2.792
2.172
2.186
1.830
1.984
2.096
2.104
2.360
2.267
2.476
1.875
1.893
1.626
1.973
1.972
2.182
2.646
1.778
2.378
1.761
2.010
2.251
1.831
2.415
2.045
2.019
                                         D-93

-------
               SU8CHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE OAyLEY  RATS
                             •  MALE ORGAM UEIGHT DATA 
-------
     SUBCHRONIC TOXICITY  OF  ORTHO-CRESOL  IN SPRAGUE DAULEY RATS
                    FEHALE ORGAN WEIGHT DATA (g)
                        [Terminal Sacrifice]
                ANIMAL  NO.   HEART   LIVER  SPLEEN  KIONEY-LFT  KIDNEY-RT
 DOSE LEVEL
 0 mg/kg/day
50 rag/kg/day
3023
3024
3025
3026
3027
3028
3029
3030
3Q31
3032
3033
3034 '"
3035
3036
3037
3038
3039
3040
3041
3042
305
-------
               SUBCHRONIC TOXICITY OF  ORTKO-CRESOL IN SPRAGUE CAWLEY RATS
                            FEMALE ORGAM WEIGHT DATA (g)
                                [Terminal Sacrifice!
                ANIMAL NO.  OVARY-LFT  QVARY-RT  ADRENALS  BRAIN  THf./PARA.  TERM. WOT.
   DOSE LEVEL
0 mg/kg/day 3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
50 mg/kg/day . 3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
0.040
0.047
0.046
0.042
0.108
0.028
0.040
0.042
0,033
0.046
0.037
0,045
0.023
0,035
• 0.033
0.026
0,060
0.045
0.025
0.037
na
0.050
0.046
0.037
0.045
0.067
0.024
0.009
0.036
0.045
0.048
0.038
0.028
0.050
0.038
0.024
0.046
0.048
0.056
0.041
0.042
0.030
0.050
0.048
0.092
0.033
0.045
0.040
0.047
0.028
0.048
0.046
0.029
0.053
0.040
0.023
0.041
0.048
0.017
0.042
na
0.038
0.039
0.036
0.042
0.064
na
0.020
0.041
0.040
0.055
0.044
0.041
0.046
0.022
0.050
0.036
0.046
0.055
0.041
0.072
0.056
0.059
0.057
0.071
0.062
0.062
0.051
0.054
0.063
0.056
0.083
0.046
0.053
0.072
0.059
O.Q78
0.060
0.052
Q.Q70
0.069
0.081
0.063
0.059
0.075
0.075
0.044
0.060
0.068
0.051
0.063
0.074
0.046
0.076
0.055
0.047
0.063
0.065
0.060
0.043
1.924
1.860
2.085
1.955
2.168
1.852
1.947
1.960
1.955
1.876
2.083
2,070
1.918
1.965
1.923
1.977
1.935
2.062
•1.915
1.940
na
2.193
2.130
1.940
1.7B5
1.995
2.128
1.851
0.872
2.022
2.130
1.951
1.790
2.099
1.887
1.836
1.893
2.061
2.027
1.764
0.035
0.020
0.035
0.024
0.019
0.020
0.026
0,021
0.021
0.013
0.029
0.015
0.017
0.034
0.015
0.032
0.032
0.026
0.030
0.027
0.017
0.024
0.021
0.022
0.014
0.023
0.025
0.034
0.022
0.036
0.026
0.025
0.024
0.032
0.019
0.017
0.021
0.017
0.017
0.027
244
262
307
245
290
265
259
245
265
257
258
254
245
252
251
267
262
254
262
234
255
316
323
279
233
290
303
273
250
328
273
310
238
310
299
300
274
249
268
303
na  =  no  data  available,
                                           D-96

-------
      SUiCHRQNIC TOX5CITY OF ORTHO-CRESOL  IN SPRAGUE DAULEY RATS
                     FEHAli ORGAN WEIGHT DATA (g)
                          [Terminal Sacrifice]
                ANLHAL NO.  HEART   LIVER  SPLiEN  KtDNEY-LFT  K10NEY-RT
 DOSE LEVEL
175 mg/kg/day
600 mg/ks/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
309S
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
3130
3135
3136
3139
0.985
0.915
0.804
1.315
1.117
0.976
0.802
0.785
0.985
0. 814
0.940
0.968
0.984
1.037
0.874
0.984
0.929
0.968
0.924
0.934
0.879
0.714
0.383
1.017
8.341
7.476
7.554
11.721
9.448
9.802
8.057
7,. 501
7.767
7.818
9,697
9. 488
8.104
B.713
7.962
9.886
8.890
7.662
7.534
8.636
7.626
7.639
7.845
9.157
0.585
0.472
0.540
0.465
0.566
0.532
0.444
0.510
0.604
0.515
0.568
0.547
0.658
0.505
0.423
0.519
0.361
0.496
0.388
0.442
0.505
0.480
0.374
0.628
1.025
1.059
0.987
1.378
1.1S9
0.942'
0.980
0.888
1.121
0.795
1.136
1.078
0.871
1.087
1.181
1.048 -
0.965
0.985
0.975
1.080
0.901
0.897
0.898
1.079
1.079
1.078
1 .034
1.455
1.219
0.961
1.008
0.946
1.199
0.898
1.150
1.129
0.876
1.710
1.062
1.181
0.973
0.965
0.962
1.106
0.931
0.970
0.939
1.046
                                        D-
                                           97

-------
              SUBCHRONIC TOXtCITY OF ORTHO-CRESOl JN SPRAGUE  DAULEY  RATS
                             fEMALE ORGAN UEIGHT DATA 
                                 [Terminal Sacrifice!
                ANIMAL NO,  QVARY-LFT  OVARY-RT  ADRENALS  BRAIN   THY./PARA.
fERH,  WGT.
 DOSE IEVEC
 175 mg/kg/day
600 mg/kg/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
310S
3106
3107
3108
3130 .
3135
3136
3139
0.034
0.027
Q.Q44
0.050
0.044
0.050
0.039
0.080
0.033
0.034
0.047
0.045
0.052
0.037
0.041
0.031
0.032
0.030
0.044
0.057
0.063
0.039
0.042
0.040
0,050
0.025
0.043
0.052
0.044
0.057
0.044
0.072
0.045
0.046
0.051
0.034
0.045
0.059
0.036
0.024
0.039
0.035
0.040
0.038
0.049
0.022
0.034
0.027
0.059
0.055
0.050
0.074
0.068
0.065
0.058
0.074
0.060
0.062
0.043
0.037
0.067
0.066
0.072
0.042
0.064
0.050
0.078
0.063
0.060
0.068
0.071
0.066
2.014
2.053
2.053
2.063
2.030
1.7S4
1.798
1.9S4
1.790
1.888
0.818
1.924
1.879
na
2.128
1.945
• 1.847
2.064
1.907
2.103
1.960
1.928
1.945
1.931
0.030
0.035
0.026
0.022
0.035
0.022
0.024
0.019
0.030
0.024
0.023
0.026
0.021
0.015
0.030
0.010
0.027
0.032
0.021
0.031
0.030
0.021
0.021
0.031
262
229
245
291
282
284
236
253
247
238
290
308
284
279
255
294
293
266
229
278
239
232
244
256
                                                D-98

-------
                            SUBCHRON1C TOXIC1TY OF ORTHO-CRESOL  IN  SPRAfiUE DAULEY RATS
                                               MALE URINALYS1S DATA
                                                [Interim Sacrifice!
                Animal no.  App.  Vol. (ml)  Sp.  Gr.   Color   pH   Protein  Glucose  Ketones  Uro.  Situ  Stood Hgb.
 DOSE LEVEL
 0. mg/ kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2881
2832
2883
2834
2885
2886
2887
2838
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2985
2986
2987
2988
2989
cl
cl
cl
cl
hz
cl
el
c
cl
hz
cl
cl
cl
cl
c
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
el
cl
cl
cl
c
c
c
cl
c
5
5
5
5
5
6
5
5
5
5
5
6
5
5
5
5
5
5
5
5
5
5
6
5
5
5
5
6
5
5
6
5
6
5
5
5
5
5
5
1.012
1.011
1.007
1.016
1.009
1.024
1.022
1.008
1.010
1.007
1.012
1.007
1.017
1.006
1.008
1.017
1.019
1.014
1.012
1.014
1.015
1.010
1.011
1.007
1.027
1.017
1.020
1.026
1.014
1.030
1.014
1.012
1.014
>1,035
1.012
1.007
1.032
1.009
1.011
s
s
s
y
s
py
y
s
s
s
y
s
s
s
s
py
s
y
5
S
S
s
py
s
y
s
s
y
s
y
py
s
s
y
y
s
y
s
s
8.0
6.5
8.0
9.0
8.0
7.0
9.0
9.0
7.5
8.0
8.0
8.0
8.0
8.0
9.0
8.0
6.S
8.0
8.0
7.0
8.0
8.0
8.0,
7.0
9.0
9.0
6.5
7.0
9.0
6.5
6.5
8.0
6.5
9.0
7.0
6.5
6.0
6.5
6.0
tr
tP
tr
1 +
tr
tr
tr
tr
ng
ng
tr
tr
1+
ng
tr
ng
ng
tr
tr
tr
tr
ng
tr
ng
1 +
tr
ng
tr
tr
tr •
tr
1+
tr
1+
tr
tr
tr
tr
ns
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
,ng
ng
ng
ng
ng
ng
ng
tr
na
ng
"9
ng
ng
ng
"3
ng
ng
1+
ng
ng
ng
ng
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
10ery\ul
ng
ng
10ery\ul
ng
ng
ng
ng
10ery\ut
ng
ng
"9
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
                                                          D-99

-------
               SUBCHRONSC TOX1CITY OF ORTHO-CRESOU  IH  SPSAGUE DAWLEY RATS
                            MALE MICROSCOPIC URINALYSIS DATA
                                   [Interim Sacrifice]
                ANIMAL NO.  RSC/HPF  USC/HPF  EPI/HPF   CASTS/LPF  CRYSTALS  YEAST  BACTERIA
 DOSE LEVEL
 0 nig/kg/day
50 mg/fcg/day
175 mg/kg/day
600 mi/kg/day
2881
2882
2883
2884
2885
2336
2337
2868
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2951
2954
2955
2956
2980
2981
2982
2983
2985
2986
2987
2988
2989
0
0
0
0
0
0
0
0
0
0
0
0
Q
Q
0
Q
0
0
0
2-3
0
0
Q
0
0
6
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
'0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0 '
0
0
0
0
0
0
0
0
0
n
n
n
tp
n
tp
n
n
tp
n
«P
tp
n
n
n
n
n
tp
tp
n
tp
n
tp
n
tp
tp
n
tp
tp
CO
tp
n
tp
tp
n
n
n
n
n
f
f
n
f
n
n
m
f
n
f
f
n
n
n
n
n
n
f
n
f
n
n
m
n
m
f
f
n
n
n
n
n
n
nun
n
f
f
f
n
num
m
f
m
f
num
num
m
f
f
m
f
f
m
m
f
m
m
nurn
mod
num
m
m
f
num
m
m
f
nun
num
m
in
m
nun
f
m
m
m
f
                                             D-1QQ

-------
                            SUBCHROMIC TOXICITY OF QRTHQ-CRESQL IN SPRAGLIE DAUIEY RATS
                                               HALE URJNAlfSlS DATA
                                               tTerm'inal Sacrifice]
                Animal no.  App.  Vol'. (ml)  Sp,-Gr,  Color   pH  Protein  Glucose  (Cetones   Uro.   Bili.  Slood Hgb,
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2994
2996
2998
2999
3001
3003
3005
3007
cl
hz
c
hz
hz
hz
el
cl
cl
hz
hz
cl
cl
hz
hz
cl
•cl
hz
hz
hz
hz
hz
c
hz
cl
hz
hz
cl
hz
hz
c
cl
hz
c
hz
c
hz
hz
hz
cl
15
14
15
15
7
15
15
15
9
15
15
9
12
15
13
15
15
14
12
15
10
14
15
15
15
15
15
15
8
10
13
15
15
15
15
15
13
15
15
14
1.030
1.027
1.012
1.019
1.025
1.023
1.028
1.026
>1.035
1.013
>1.035
>1.035
1.019
1.018
1.021
1.035
1.012
1.021
1.014
1.033
1.032
1.030
1.022
1.025
1.030
1.016
1.014
1.013
>1.035
>1.035
1.029
1.020
1.019
>1.035
1.032
1.023
>1.035
1.017
1.025
1.030
y
y
s
y
y
y
y
a
y
s
s
y
6
S
y
y
a
y
a
y
y
y
s
y
y
s
s
a
S
a
y
s
s
Y
s
a
y
s
s
y
6.0
7.0
8.0
9.0
6.0
7.0
8.0
7.5
6.0
9.0
7.5
9.0
8.0
9.0
8.0
9.0
7.0
6.5
6.5
7.0
7.0
5.5
7.0
8.0
7.0
9.0
7.5
9.0
6.0
6.0
9,0
9.0
7.5
5.0
6.5
5.0
6.0
7.5
6.5
6.0
1+
2+
* tr
1 +
1+
2+
2+
1+
2+
1+
1+
1+
1 +
ng
tr
2+
1 +
1+
1+
1+
1*
tr
1+
2+
2+
1+
2+
2+
2+
2+
2+
2+
tr
1+
2+
tr
tr
2+
ng
tr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr ,
nr
nr
nr"
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
"9
ng
1+
ng
1 +
ng
1+
ng
ng
ng
ng
ng
ng
1 +
ng
1 +
1+
ng
ng
ng
ng
ng
ng
ng
ng
ns
1 +
ng
ng
ng
ng
1+
1 +
1*
1 +
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ns
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ns
ng ,
ng
ng
ng
ng
ng
ng
ng
- ng
ng
10ery\ul
ng
ng
ng
ng
10ery\ul
ns
ng
ng
ng
ng
1Qery\ul
ng
ng
50ery\'jl
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
                                                          D-101

-------
               SlJaCHRQNlC TOXICITY OF ORTHO-CRESOL  IN  SPRAGUi DftUlET RftTS
                            MALE MICROSCOPIC  URINALYS1S DATA
                                  [TERMINAL SACRIFICE]
                AMIMAL NO,   R3C/HPF  USC/HPF   EPI/HPF  CASTS/LPF  CRYSTALS  YEAST  BACTERIA
 DOSE LEVEL~
 0 mg/kg/day
50 mg/kg/day
175 mg/ks/day
600 mg/kg/day
2891
Z892
2893
2894
2895
2896
2897
2S9S
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2994
2996
2998
2999
3001
3003
3005
3007
0
0
0
0
0
•2-3
0
0
0
0
0
'0-1
"0-1
0
0
0
0
0
0
•2-3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
•1-2
0
0
0
0
0
0
•2-3
0
0
0
0
.0
0
0
0
0
0
0
0
•0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
' 0
0
0
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
0
CO
CD
tp
tp
CO
tp
tp
n
CO
tp
n
tp
n
tp
tp
tp
CO
CO
co\tp
co\tp
tp
CO
tp\eo
tp\co
CO
tp
CO
tp
tp
co\tp
tp
tp
CO
CO
CO
co
CO
n
n
CD
f
f
n
n
n
f
n
n
n
f
n
n
n
n
m
m
n
. n
f
f
n
f
n
n
n
f
f
f
n
n
n
n
f
n .
m
1
n
f
n
n
m
m
f
f
m
m
n
m
f
f
f
m
f
m
n
n
n
n
f
n
m
m
n
n
f
f
m
nun
ID
f
f
f
n
f
m
f
f
m
nura
f
                                             D-102

-------
                            SUSCHRONtC TOXICITY  OF  ORTHO-CRESOL  IN SPRAGUE DAWLEY RATS
                                              FEMALE  UR1NALYS1S  DATA
                                                (Interim  Sacrifice]
                Animal tio.  App.  Vol.  (ml)  Sp.  Gr.   Color   pH  Protein  Glucose  Ketones  Uro.  Bili.   Blood Kgb,
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
3013
3014
3015
3016
, 3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
30B2
3083
3084
3085
3086
3087
3088
3114
3115
3116
3117
3118
3119
3120
cl
cl
hz
cl
cl
c
cl
cl
cl
cl
c
cl
c
cl
cl
cl
cl
cl
el
c
cl
hz
cl
c
cl
cl
cl
cl
cl
cl
cl
c
cl
c
cl
cl
cl
5
5
5
5
5,
5
5
5
5
5
5
5
5
6
5
5
5
5
5'
6
5
5
5
6
5
5
5
5
5
5
5
5
6
5
5
5
5
1.023
1.012
1.006
1.029
1.037
1.027
1.014
1.016
1.015
1.026
1.014
1.018
1.010
1.015
1.014
1,016
1.028
1.009
1.022
1.008
1.012
1.007
1.017
1.009
1.016
1.011
1.016
1.010
1.008
1.011
1.019
1.020
1.019
1.006
1.016
1.014
1.015
py
s
s
y
y
y
s
s
s
py
s
py
s
py
y
py
y
s
y
s
s
s
s
s
s
s
s
s
y
s
y
y
py
s
py
y
py .
8.0
7.0
8.0
9.0
8.0
6.0
7.0
8.0
9.0
9.0
9.0
9.0
6.5
8.0
8.0
9.0
8.0
8.0
9.0
6.5
7.0
8.0
9.0
6.5
7.0
7.0
8.0
6.5
8.0
9.0
8.0
6.0
6.0
8.0
9.0
9.0
6.5
tr
ng
"ng
tr
2+
ng
tr
tr
ng
"3
ng
tr
tr
ng
tr
ng
1+ .
ng
tr
ng
tr
ng
ng
ng
tr
tr
tr
tr
ng
tr
ng
ng
ng
ng
ng
tr
tr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
1+
ng
tr
ng
tr
ng
tr
ng
ng
tr
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
«9
                                                      D-103

-------
               SU8CHRONIC TQXICITY  OF  ORTHO-CRESOL IN SPRAGUE DAHLEY RATS
                           FEMALE MICROSCOPIC URINALYSIS DATA
                                   [Interim Sacri f ice]
                ANIMAL  NO.   R8C/HPF   WBC/HPF  EPi/HPF  CASTS/LPF  CRYSTALS  YEAST  BACTERIA
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
175 rng/kg day
600 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3034
3085
3086
3087
3088
3114
3115
3116
3117
3118
3119
3120
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
• 0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
Q
0
0
0
•0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
" 0
0
0
• Q
0
0
Q
0
Q
0
0
0
0
o
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
n
tp
n
tp
tp
n
n
tp
n
tp
tp
n
n
tp
tp
tp
tp
n
tp
n
n
tp
tp
n
«P
n
n
n
tp
tp
n
n
n
n
n
tp
CO
f
n
n
n
f
n
n
f
n
n
n
n
n
f
m
n
m
m
m
n
n
f
n
n
f
n
n
f
n
f
f
f
n
f
n
f
f
n
m
f
m
num
f
m
nun
m
m
f
m
f
m
num
m
n
m
num
f
m
m
f
f
m
m
f
f
m
f
n
f
•f
n
m
f
f
                                        D-104

-------
                            SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                                              FEMALE URINAIYSIS DATA
                                               [Terminal Sacrifice]
                Animal no,   App.   Vol.  (ml)   Sp.  Gr.   Color   pH  Protein  Glucose  Ketones  Uro.  Bill.  Blood Hgb.
 DOSE LEVEL
 0 mg/kg/day
50 fag/kg/day
175 mg/kg/day
600 rag/kg/day
3023
3025
3026
3027
30Z8
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3130
3135
3136
3139
hz
c
hz
hz
c
hz
c
c
c
cl
hz
hz
c
c
hz
c
hz
hz
hz
cl
hz
hz
c
hz
cl
hz
hz
cl
c
e
c
c
hz
12
13
9
13
2
14
4
13
9
6
15
12
15
15
14'
4
13
14
14
11
5
5
10
5
15
15
15
11
13
14
15
10
15
1.021
1.011
1.022
1.028
>1.035
1.025
>1.035
1.026
>1.035
>1.035
>1.035
1.035
1.027
1.009
1.017
1.031
1.015
1.016
1.024
1.013
>1.035
1.032
>1.035
>1.035
1.016
1.014
1.019
1.013
1.018
1.027
1.020
1.019
1.024
y
y
y
y
y
s
y
8
y
y
s
y
y
s
y
y
s
y
y
a
y
Y
y
y
s
s
iy
y
iy
• s
s
y
s
7.0
6.5
5.5
9.0
5.5
9.0
8.0
6.5
6.0
9.0
7.0
9.0
6.5
9.0
9.0
5.6
7.0
7.0
6.5
9.0
5.5
7.5
6.0
6.0
9.0
6.5
6.0
9.0
6.0
6.0
6.0
8,0
5.5
tr
ng
• tr
2+
1+
ng
2+
tr
1 +
2+
tr
2+
tr
ng
1+
tr
lr
tr
ng
1 +
tr
ng
2+
2+
1+
ng
tr
1+
1+
tr
1+
tr
1+
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
1*
ng
1+
ng
1+
ng
"9
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
1 +
1*
1+
ng
ng
ng
ng
ng
1+
1 +
"9
1+
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
"9
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
10ery\ul
ng
ng
ng
ng
ng
1Cery\ul
ng
ng
ng
ng
"3
ng
ng
ng
                                                       D-105

-------
               SUBCHRONIC TCX1CITY QF  ORTHO-CRESOL  IN SPRAGUE DAUltT RATS
                           FEMALI  MICROSCOPIC UR1NALYSIS DATA
                                  [TERMINAL SACRIFICE]
                ANIMAL MO.   R3C/HPF   HBC/HPF  EPJ/HPF  CASTS/LPF  CRYSTALS  YEAST  BACTERIA
 DOSE LEVEL"
 0 mg/kg/day•
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
3023
, 3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3130 '
3135
3136
3139
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
o •
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
• 0-1
0
0
'0-1
'1-2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CO
CO
CO
tp
CO " '
tp
tp
CO
tp
co\tp
co\tp
' tp
CO
tp
CO
n
co\tp
CO
co\tp
tp
CO
tp
CO
n
CO
n
CO
tp
tp
tp
CO
tp
n
f
f
n
n
n
f
n
f
f
n
n
n
f
n
n
n
n
n
n
n
n
m
n
n
n
f
f
f
f
n
m
m
n
m
m
n
f
f
m
f
f
m
m
f
f
f
f
f
m
f
m
f
n
f
n
f
f
m
m
m
f
m
f
f
f
f
                                          D-106

-------
                             Study No. 5221.06
     APPENDIX E




OHfTH&IMODDGY REPORT
       E-l

-------

-------
                                                       Study No. 5221.06
                     SUBCH8DNIC TOXtem OF ORIHO-CHESOL
                            IN SPRAGUE DAWLEY EATS

                             ABBREVIATION CODES
Eve Examinations

rtvl  = no visible lesions
dead = unscheduled death
A    = os (left eye) early retinal degeneration
B    = focal retinal degeneration
na   = no data available
                                       E-2

-------

-------
EY £ • C L I N 1C
F Q g • A N I M_A_L j
                                                                       2 4  .1985
               Nancy M. Bromberg, V.M.D., M.S.
               Qiotomate, American College of Veterinary Ophthalmologists
               41(55 Brandywine Street, Northwest
               Washington'D.C. 20016
               202/383^303
   Barry  S.  Levine
   Microbiological Associates  Inc.
   5221 River Road
       esda,  BD  20816-
   SUBJECT:   Study  #5221.06

   OPHTHALMIC
   FINDINGS;
240  Sprague-Dawley  rats  (120 male,  120
ophthalmoscopically  examined Sept.  13,
No Visible  Lesions  identified
                                                        female}
                                                        1985 -
                                         E-3

-------
               Nancy M. Bromberg, V.M;D., M.S.
               Diplomats, American College of Veterinary Ophthalmologists
               4105 Brandywine Slreet, Northwest
               Washington, D,C. 20C16
               202/363-7303
EYE
           C
FOR'ANIMAIS
                                     January 2 ,  1986
   Barry S.  Levine, D.Sc.,  DABT
   Microbiological Associates Inc.
   5221 River  Road
   Bethesda, MD   20816

   SUBJECT:  Oph thalmoscopic  Evaluation  of Rats.,
             Study 5221.06  December  19,  1985
   Abnormalities  Identified:   Rat 2938,  male group  II  -  early
                                generalized  retinal degeneration Os
                                Rat 3058,  female group  II
                                focal  area of retinal  degeneration  Os
         Due  to  the infrequent and uni-ocular occurrence of. the
   abnormalities,  I do not  believe them  to be compound-related.

   All other  animals examined  had no  visible lesions.

                                           A
Naricy ^KT  B/*omberg,  V.
Dip, , JWC/V.O.
                                                              D., M.S.
                                       E-4  .

-------
                                 MEMORANDUM

                                                       December 9,  1986

TO     :   File Study No. 5221.06

FROM   :   Barry Devine  wl^

SUBJECT:   Qphttialmoscopic Examination

          Terminal ophthalmoscopic examination was on 12/12/85 as reported in
          the raw data evaluation form of 12/12/85 signed by Dr.  Bromberg.
          Her letter of 1/2/86 inadvertently gives the examination  date  as
          12/19/85.

          Dr. Bromberg's letter of I/2/B6 also misdesignated animal number
          2938, male group II as having early generalized retinal
          degeneration, whereas the raw data evaluation form, signed and dated
          12/12/85 gives this observation for animal number 2939.
                                      E-4a

-------

-------
                     SUBCHROMIC  TQXICITY QF ORTHQ-CRESQL 1M SPRAGUE DAWLEY RATS
                                       HALE  EYE EXAMINATIONS
                Animal  no.   PRETEST-Right Eye  PRETEST-left Eye  TERMSHAL-Right Eye  TERHINAl-Left Eye
 OOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
2881*
2882
2883
2834
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901 '
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvi
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl •
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
-na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
                                           E-5

-------
                    SUBCHRQNIC  TCXICm OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
                                      HALE EYE EXAMINATIONS
               Animal  no.   PRETEST-Right Eye  PRETEST-Left Eye  TERMINAL-Right Eye  TESHINAL-Left  Eye
DOSE LEVEL
50 mg/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl ,
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvi
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl "
nvl
nvt
nvl
nvl
nvl
nvt
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
A
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl .
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
                                          E-6

-------
                     SUBCHRONIC TOXICITY OF ORTHO-CRESQL IN SPRAGUE DAWLEY RATS
                                       MALE EYE EXAMINATIONS
                Animal  no.   PRETEST-Right Eye  PRETEST-left Eye  TERMINAL-Right Eye  TERHINAL-Left Eye
 DOSE LEVEL

600 mg/kg/day
2980
2981
2982
2983
2984
2985
2956
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
nvl
nvl
nvl
•nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl . -
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
dead
dead
nvl
dead
nvl '
dead
nvl
nvl
dead
nvl
nvl
nvl
dead
RVl
dead
nvl
dead ,
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
dead
dead
nvl
dead
nvl
dead
nvl
nvl
dead
nvl
nvl
nvl
dead
nvl
dead
nvl
dead
nvl
                                           E-7

-------
                     SUBCHRONIC TOXICITY OF ORTHC-CSESOL  IM  SPRACUE  DAWLEY RATS
                                       FEHALE EYE EXAMINATION
                Animal no.  PRETEST-Right Eye  PRETEST-Left  Eye   TEftMINAL-Right Eye  TERMlNAL-Left Eye
 DOSE LEVEL
 0 mg/kg/day
50 mg/kg/day
'3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
r.vl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
. nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
'na
na
na
na
na
nvl
nvl
8
nvl
nvl
nvl
                                           E-8

-------
                    SUBCHRONIC TOXICITY OF QRTHG-CRESQl IN SPRAGUE  DAULEY  RATS
                                     FEHALE EYE EXAMINATION
               Animal  no.   PRETEST-Rigbt Eye  PRETEST-Left Eye  TERMINAL-Right Eye  TERHiNAL-Left Eye
DOSE LEVEL
50 mg/ kg/day 3062
(continued) _*306J
3064
3065
3066
3067
3Q6S
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
.nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na .
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
                                                E-9

-------
                     SU8CHRON1C TOXICITY OF ORTHO-CRESOl  IN  SPRAGUE DAWLEY RATS
                                      FEMALE EYE EXAMINATION
                Animal  no.  PRETEST-Right Eye  PRETEST-Left  Eye   TERMINAL-ftight Eye  TERMIHAL-Left  Eye
 DOSE LEVEL

600 mg/kg/day
3112
-3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl1
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
dead
dead
dead
dead
nvl
nvl
dead
dead
nvl
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
nvl
nvl
nvl
dead
dead
dead
dead
nvl
nvt
dead
dead
nvl
dead
dead
                                            £-10

-------
   APPENDIX F




PATHOUDGY REPORT
  F-;
                            Study No.  5221.06

-------

-------
                    TABLE OF CONTENTS
                                            PAGE

 I. PATHOLOGY NARRATIVE                      1-1

 1!. PROJECT SUMMARY TABLE                    11-1

ill. TABULATED ANIMAL DATA                    111-1

IV. GROSS VS. MICROSCOPIC FINDINGS
    Terminal Sacrifice                        IV-1
    Interim Sacrifice                         IV-48

 V, QUALITY ASSURANCE REPORT                 V-1

   APPENDIX  1 REPORTS CODE TABLE
   APPENDIX 2 ABBREVIATION LIST

-------

-------
Pathology Associates,  Inc.
IjamsviHe, m-.
    (301) 663-1644
            SUBCHRONIC TOX1CITY OF ORTHQ-CRESOL
                 IN5PRAGUEDAWLEYRAT5
                      PREPARED FOR
             MICROBIOLOGICAL ASSOCIATES, INC

-------

-------
PATHOLOGY NARRATIVE

-------

-------
               SUBCHRONIC  TOXICITY OF ORTHO-CRESOL
                        IN SPRAGUE  DAWLEY  RATS
                         Experiment No. 5221.06

                           PATHOLOGY REPORT
                      INTRODUCTION  AND METHODS
      A  13 week gavage  study was conducted on  Sprague Dawley rats to
determine the toxlcity of o-cresol  Male and female rats were divided Into 5
groups at study initiation;
                                    Dose Level            Num ber of An i mals
            Treatment               ( mg/kg/day)           Mala        _Fero.alB
    1       Negative Control           Vehicle only           30*           30*
    2       o-cresol                    50               30*           30*
    3       o-cresol                   175               30*           30*
    4       o-cresol                   600               30*           30*
    5       Baseline clinical             ----              10**         10**
            pathology

   * 10 animals sacrificed during test week seven( interim sacrifice); 20 sacrificed at 1 3 weeks
   for histopatholog^ with 1 0 having blood collected for clinical patholog^ terminal sacrifice)
   **Sacriffced prior tostucfy Initiation

      Animals were gavaged  daily,  7 days a week,  for 13 weeks with 0, 50,
175, or 600 mg/kg of o-cresol  in a corn-oil vehicle at 5 ml/kg body weight
At the interim sacrifice, all scheduled rats were killed  using carbon dioxide
gas and  were  necropsled. All  required  tissues  (see  below) were fixed In
formalin for possible future evaluation.  At the 13 weeks terminal sacrifice,
all surviving rats were killed using carbon dioxide gas and were necropsied,
Body and organ weights  (heart, liver, spleen, brain,  kidneys [individually],
gonads [individually], adrenals, and thyroids/parathyroids),  were recorded for
all rats  at terminal  sacrifice.   AH tissues  specified by the protocol were
fixed in  10%  neutral  buffered formalin:  all  gross lesions, brain,  eyes,
pituitary, salivary glands, heart, thymus, thyroids (with parathyroids), lungs
(with  mafnstem  bronchi), trachea, esophagus,  stomach,  small  and  large
Intestines,  adrenals,  pancreas,  liver,  kidneys, urinary  bladder, testes,
prostate,  ovaries,   corpus  and cervix uteri,  spleen, bone (with marrow),
skeletal muscle, lymph node, spinal  cord,  mammary gland/skin, aorta, sciatic
nerve.

                                     1-1

-------
      Fixed  tissues  were  trimmed,  dehydrated,  embedded  in paraffin,
sectioned at Sum and stained with  hematoxyiin  and eosin.  Representative
sections were  examined from all control, mid (175 mg/kg) and high (600
mg/kg) dose rats^of both sexes (due  to a high early death rate in  600 mg/kg
dose rats, all  mid dose rats'had complete hlstopathologic examinations).
Gross lesions from low dose (50 mg/kg) terminal sacrifice rats and from
Interim sacrifice rats were evaluated and are listed  in table form In  Section
IV  of  this  report  (GROSS  VS.  MICROSCOPIC FINDINGS).   Since complete
histopathologic  examinations were required by protocol on all early death
rats and since the terminal  sacrifice high dose  animals had several early
deaths, one early death high dose male (*2984) and  3 early death high dose
females (*3H2, *3113, *3121) originally scheduled for the 7 week  interim
sacrifice  were  tabulated with  the  13 week   terminal  sacrifice  rats,
Additionally, potential  target  organs (kidney  in male and female)  were
evaluated for all low dose (50mg/kg) rats,

      Results from all complete hlstopathologic examinations as well as all
target  organs In low  dose  terminal sacrifice rats were recorded  Into a
computer which required an accounting for every organ listed  in the protocol.
The computer generated tables  are  included In  Sections II and  ill  of this
report (PROJECT SUMMARY TABLE and TABULATED ANIMAL DATA).

                               RESULTS

      Kidney was considered a potential  target organ since a slight Increase
In Incidence of  minimal renal nephropathy (minimal nephropathy consisted of
2 or more tubules  with degeneration/regeneration and  interstitial-foci of
chronic Inflammatory cells) was noted  in the mid dose rats (15 mid dose
males compared to 10 control males, and  3 mid dose females compared to 5
control female). Findings at all  dose levels, however, were not statistically
significant by Fishers Exact Test.

      Certain lesions noted in the lung of both control and dosed rats were
suggestive of infection with an adventitious agent These lesions consisted of
perivascular lymphocytlc infiltrate, and scattered foci of Interstitial  chronic
inflammation. No specific etlological agent was noted.

      Twenty-eight early  deaths occurred In high dose rats:  19 high dose
females (3 of these rats were originally scheduled for the interim sacrifice)
                                 1-2

-------
and 9 high dose  males (1 of these rats was originally  scheduled for the
Interim sacrifice).  Pulmonary lesfons noted in these early death animals are
summarized;
                                      Higft dose                High dosa
                                        Male    .               Female
    Oildroplets(minimal tomoderate)           8/9                   15/19
    Congestion (mild to moderate)               8/9                  .14/19
  .  Edema (minimal to severs)                 6/9    .               16/19
    Hemorrhage (minimal)                    2/9*   "               S/19

      * Two additional high dose males surviving to final sacrifice also had minimal to mild
    pulmonary hemorrhage (total of 4).

      Clinical  observation records were  reviewed.  Death in the majority of
these animals  was probably related to lung lesions.  These lesions, however,
were considered to be secondary to clinically-noted neurological signs rather
than due to gavage/technician error for the following reasons.  There was no
evidence  of  esophageal  or  trachea!   tears   and   tracheal  inflammation/
hemorrhage was evident only In 1 rat  Deaths occurred only in high dose rats.
Clinical observations of tremors, convulsions and comatose condition shortly
after dosing were noted  No foreign body pneumonia (frequent consequence of
gavage error) was noted-except  in one high dose female rat (*3I35) which
showed typical clinical  signs of gavage error (oil around mouth and gasping
after dosing) and  in 2 vehicle  males (all  three of these rats survived  to
terminal sacrifice).

      A  few  lesions  (increase  In  mandibular  lymph node  congestion and
hemorrhage, liver congestion) in  these high  dose animals wert interpreted as
consequences  of  spontaneous death.   Other  lesions  (decrease  In  splenic
hemosiderosis  and chronic hepatic inflammation) were  related to presence of
mild autolysis  or  early death in  these high dose rats.  None of these lesions
was considered significant

      Additional  lesions were of low  incidence and/or equally distributed
between control  and dosed animals and  were considered  incidental lesions
commonly seen in  this age and strain of rat
                               1-3

-------
                      SUMMARY  AND CONCLUSIONS

      Sprague Dawley rats of both sexes were gavaged once a  day, 7 days a
week for 13 weeks with 0, 50, 175, or 600 mg/kg of o-cresol  in  a  corn-oil
vehicle.

      Lesions noted  In  the  lung of both  control  and dosed  rats were
suggestive of infection with an adventitious agent.  No specific etiological
agent was noted.

      Early deaths occurred  in 9 high dose males  (1  of  these rats was
initially scheduled for interim sacrifice) and 19 high dose females (3  of these
rats were initially scheduled for  interim  sacrifice).   Lung  lesions  (oil
droplets,  congestion,  edema) noted in  these  rats  may   have  been  the
consequence of aspiration due to convulsions which occurred  after dosing.  No
neuropathology was evident for these clinically noted,  apparent compound-
and dose-related neurological effects.

      In conclusion, no target organ was  apparent   Early  deaths were
associated with clinically  observed neurological signs without evidence of
neuropathology.
                                     Diana S. Copeland, D.VJ1
                                     Dlplomate, A.C.V.P.
                                     May 23, 1986
                                 1-4

-------
II.  PROJECT SUMMARY TABLE

-------

-------
PATHOLOGY  ASSOCIATES,   INC.

                     ORTHO-CRESQL
                   STUDY NO. 5221.04
                  SPRAGUE-imEY RATS
Pr
SimW: Incidence
PROJECT ID'. NO: OCRESfll
DAYS; ALL
GROUP:
NUMBER OF AN1WAIS:

KWIN
SCIATIC NERME
SPIWL CORO
HUE
BONE WRROU
SAL1WRV ilANQ
LWHflCYTIC INFILTRATE
HflNOIIUWR LWH NODE
CDN5ESTIDN
ITWPHOJO HffERPLASW
Timiys
mORRWSE, ACUTE
n^CREAS
LWPHOCfTIC IHF1L7W7E
HiMOSIOEROSJS
oject Summary Table
a-f NEOPWST3C and MW-NEDPWSTIC
MTES: AH
SEX; MALE
O.OHS/KG 50 HS.KG
20 20
1 1
i Ex 20 8
1 Ex 20 D
1 Ex 20 0
i Ex 2J 0
1 Ex 20 0
I Ex 20 0
0 0
1 Ex 20 0
a o
? 0
1 EJ 20 C
id 0
1 Ex 20 0
0 0
2 0
INFWM^TJOH, CHRDN1C-ACI1VE 1 0
ACIWR ATRDPHf
PITUITARY
CYiT


1 0
1 Ex 20 0
a o
(Sfcport Continued)
II-l
Microscopic


17*BXK6
20
,
20
• 20
20
20
20
20
i
28
0
?
2fl
U
20
1
0
1
I
20
1


Finding!


500MG/KS
21
,
2!
21
21
21
21
20
(1
20
3
9
20
1?
1?
5
i
0
0
21
0



-------
  ASSOCIATES

    DSTHO-CRESOL
 STUDY NO. 5221.06
$?RA6UE-DAUL£Y RATS
INC
Proj e
c t Summar
y
Tabl e
SUHSRY: Incidenc* of HEOPLAST1C and NON-NEOPLASTIC Microscopic
PROJECT ID-: NO: OCRESOL
DAYS: ALL
GROUP;
MJ1BER OF (WIHALS:

THYROID
EPITHELIAL CYST
LWHOCYTIC INFILTRATE
INFWtWriGN, GMNULiMIQUS
PARATHYROID
TRACHEA
LYNPHOCYT1C INFILTRATE
03N6EST1DN
INFLATION, ACUTE
DILATION, GLANDS
ESOPHAGUS
INFLAmVHON, CHRONIC
AOSEWL SLAW
ECTASIA, HEBULW
LLN6
LYNPKOCYTIC ]NF1LTRATE,PERJV
1WW, lOTERfTlTIAL CHRONIC
OIL DROPLETS
CONGESTION
EM»
HEMRRWiGE
OSSEOUS METAPLASIA
MINE1MLJ2ATION, UESSEL
HlSTIOCYTOSiS
PNEIHONIA, FOREIW iflDY
M. HYPERTROPHY, VESSELS
MCTERIA
HMfTT
INFWitMTION. CHRCK1C
FATES: AH
SEX; mil
fl.OMtt/KB SO
2Q
1
i Ex 20 '
10
1
0
1 Ex 1?
1 Ex 20
I
0
0
0
t Ei 20
a
1 Ex 20
4
I Ex 20
13
9
0
0
0
0
0
0
2
2
Q
0
1 Ex 20
10


KG
2(3
i
0
0
fl
a
0
g
0
9
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
fl
0


•KG I7TO/KQ
20
1
20
11
i
0
20
2tt
1
0
0
I
19
0
20
?
20
i?
11
0
0
0
0
i
2
1
1
0
0
20
12

Findings


430MS/KS
21
I
20
9
2
1 -
20
20
1
1
t
0
21
2
21
3
21
U
7
8
8
t,
4
9
8
5
0
1
1
21
3
       II-2

(Rtporl Continued)

-------
r-r-i * ii -^j


Pr
SlftlARY; Incidence
PROJECT 10," NO: OCRESOL
MYS: ALL
GROUP:
NUHEi OF iWNftlSi

AORTA
COLON
DUQDENU1
F8RESWMCH
GLANDULAR STOHflCH
DILATION, SUM)
SKIN
fWfUWf 6Lf«D
SKELETAL MU1CLE
LIMER
INWRCT, WUWTE LOSE
FIBROSIS
CON6ESTION
IHFWtWTlflN, CHRONIC
NECROSIS, CM6ULATWE
LYWHOCTTIC INFILTRATE
SPLEEN
HEMOSIDEROSIS
EMH
CYST


ora-CRisoi
STUDY NO, 5221, Da
SPRAGUE-OrWLEY RATS
oject Summary Tal
of NEOPWST1C ind NCN-WEDPLASTIC
FATES; ALL
SDC; mif
O.OHG/KG 50 HG.KG
20 20
1 i
* Ex 20 0
1 Ei 20 0
1 Ex 20 0
i Ex 20 fl
1 Ex 20 0
I I
1 Ex 20 8
1 Ex U 0
1 Ex 20 0
1 Ex 20 0
o a
i 0
0 0
3 0
i 0
0 . 0
1 Ex 20 0
10 0
a o
i 0
(Report Continutdl
II-3
1 INt*. .


bl e
Microscopic


I73WXG -
20
1
20
29
20
20
20
0
20
H
2D
20
1
0
0
3
fl
1
2D
10
0
0






Findings


dWNB/ra
21
i
21
20
1?
2S
21
2
2S
IS
21
21
i
0
3
i
1
1
2J
8
1
0



-------
              PATHULOUY  AisSOCl A I  tb ,

                                  OKTHO-CRESOL
                                STUDY NO.  5223 ,U
                               SPfWGUE-MULEY RATS
Pr o j e
c t Summar
X
Tab! e
SIMttRY; Incidence of NEOPWST1C and NON-NEOPLAST1C Microscopic
PROJECT 10, NO: OCRESOL
DAYS; ALL
GROUP:
NU18ER OF ANIHALS:

KIDNEY
NEPHROPATHY, CHRONIC
INFLATION, ACUTE, PELVIS
LWHQCYT1C INFILTRATE
mmmmmm
URINARY BLADDER
LWHQCYT1C INFILTRATE
CALCULUS
TESIES
ATROPHY, SffllNlFEROUS TUiULE
IffPERPWSift, IKTERSTIT, CELL
PROSTATE
LYHPHOCYTIC INFILTMTi
DUftfff
UTERUS
EYES
CATAIWCT, LENS
RETJfttL ATSOPHY
FATES; All
SEXs MALE
8.0HG/KG 39
20
i
I Ex 20
10
0
2
D
i Ex 20
J
6
f Ex 20
i
0
t Ex 20
11
* Ex -8
1 Es J
* Es 28
8
9


MS.
2D
i
20
9
i
6
i
0
0
0
1
1
i
0
•0
0
(1
0
0
0


KG 17WKS
20
tt
20
15
0
2
0
20
2
3
20
0
ft
20
10
0
9
20
0
i

Findings


iflBMG/KG
21
1
21
i
0
0-
0
21
1
3
21
1
0
21
4
1
5
21
1
9
CERVIX
                               (Report Continued)
                                      'II-4

-------
              PATHOLOGY _ASbOClm"r tS ,

                                 CCTHO-CRESQL
                               STUDY NO, 5221.04
                              SPRAGUE-OflULEY IWTS
                   Project   Summary  Table
           :  Incidence  si NEOPWSTiC  jnd NON-tiEQPLASTlC Microscopic Findings
PROJECT ID, NO: OCRESOL              FATESr AIL
              MS:  ALL        SEX: HALE

6MHIPI                         O.OM5/K8    50 HE.Kfi    I75HG/K6
NUMBER OF (SNIWLS;                20         20          20          21
OTHER TISSUES WO LESIONS;

HESENIER1C LN-HEMORRHASE            1          J          0
JN6. LN-LWHOID HYPERPWSIA        1          I          0
           r NEO!OS1S              I          D          1
                                      II-5

-------
                        IMC
   ORTHO-CRESOL
 STUDY NO, 5221, U
SPM6UE-MULEY RATS
Project Summary Table
SUftWlY: Incidence of NEflPLASTIC and NCN-NEOPWSTIC Microscopic Findings
PROJECT ID-i NO: OCRESOL
DAYS! ALL
GROUP:
NUMBER OF ANIMALS:
ifWIN
SCIATIC NERVE
SPIfML CQRO
SINE
i!NE mfiROU
SALIWRY GUWCI
NWQIiULAR LWPH NODE
ffiMORIWIBE, «UTE
CONGESTION
IWPH010 HffERPLASM
THWUS
ifHORSHABE, ACUTE
CYST
WNWWS
LWPHOCYT1C INF1LTMTE
fCimt ATROPHY
PITUlTflRY
RST
FATES: fill
SEX; FEWLE
0,flMG/KB 50
20
i
1 Ex 20
1 Ex 20
II Ex 20
1 Ei 20
1 E> 20
I Ex 20
1 Ex 29
3
0
12
lEx 20
13
0
1 Ex 20
3
1
1 Ex 20
0

HG/KO,,
20
H
0
0
0
D
0
0
0
0
0
0
0 •
0
(i
0
0
0
0
0

1731G/KG
20
It
20
20
20
21
20
. 20
2J
0
9
J5
n
16
1
20
2
2
*2fl
1

6DHM5/KB
23
1
22
23
22
23 .
a
23
22
i
7
13
21
14
, 1
21
i
J
22
0
(Report Continued)

II -6




-------
              PAl"rlUL.Uu*f
                                               i t is
                                  OTHMRESOL
                                STUDY NO. 3221. Oi
                               SPRAGUMJAULR RATS
Pr o j e
c t Summar
y Tab! e
SUTOMYi Incidence oi NEOPLASTY and NQN-NEOPLASTIC
PSOJECT ID" NO: OCRESOL
DAYS: ALL
GROyP:
NIW8ER DFOTWLSs

TKYRQID
EPITHELIAL CYST
LYHPHQCY11C INFILTRATE
MRATHYRDID
TOCHEA
LYMPHOCYTE INFILTRATE
(€HflRRW6i, ACUTE
INFLATION, ACUTE
ESQPWiUS
IWUWffHH, CHHON1C
«RE*L SUttC
ECTASW, MEDULLA
LUNS
LWPHOCYTIC IhFILTTWT£,PE8W
1NF1A1, IHTERSTHML CHRWIC
OIL DIOPLETS
CON6ESI10N
EDEMA
HEMORiJWBE
HI5TIOCYTOSIS
PNEDMIWIA, FORIION BODY
PNEUMONW, CHRONIC-ACTWE
WCTE8W
mm
IHFWtttTlON. CHRONIC
Microscopic
Findings
WES: ALL
SEX: FHW.E
O.QHG/KB 50
20
„
it EX n
13
0
1 Ex IS
1 Ex 21
5
0
0
1 E* 18
0
1 Ex 21!
3
i Ex 2C
I?
8
1
0
0
0
9
0
9
0
II Ex 20
2

HG/KG
20
8
0
I
9
0
0
0
0
0
0
0
g
0
0
0
0
0
1]
0
9
a
0
0
a
0
0

17WK5
20
i
2J
ti
i
U
28
2
8
D
20
fl
20
i
20
20
(,
e
0
a
D
3
0
0
0
20
3

mwm
23
1
22
11
2
18
21
t
S
i
23
i
22
2
23
14
7
15
14
H
5
2
1
2
1
23
I
flflRTA
1 El  20
                                                         20
23
                                      II-7
                               (Report Continued)

-------
   WTHO-CRESOL
 STUDY NO. 5221.OS
SPRAGUE-MULEY RflTS
Proj
e c t Sumrnar
y Tabl e
SlttWIN: tncidsnci a* NEOPLMTIC and NQN-NE0PLASTIC
PSDJEET IttC NO; flCRESOL
MYS; ALL
GROUP;
WH3ER OF (WmiS:

COLON
KIODENUK
FOiESTQfttCH
CONSKT10N
GWNOUWR STUWCH
SK1H
fWtWfiTf GUWD
SCELETAL MUSCLE
LIVER
C8N6ESTICN
lNFUWWn», CHRONIC
LWHWrniC INFILTRATE
L1PIDOSIS
SPLEEN
H81QSIDEROSIS
FftTES: fill
SEX: FEhWLE
O.CMG/KG 50
20
,
1 Ex 20
I Ex 20
1 Ex 20
2
1 Ex 20
1 Ex 20
1 Ex 28
i Ex 20
t Ex 20
0
7
9
1
4 Ex 20
lo


HE/KG
20
i
0
0
1)
0
a
0
3
D
0
0
0
0
i
0
0
Microscopic


17WKG
20
I
20
20
2fl
1
20
2D
20
20
20
g
2
I
9
20
15
Findings


MOMS/KS
23
,
21
1?
23
a
23
23
23
23
23
3
t
1
1!
21
7
(Report Continued)
        11-8

-------
                                  KTHO-CRESQL
                                STUDY NO, 5221.06
                               SPWGUE-MULEY SATS
Pr oj e
c t Summar
y Tabl e .
SUttttRY: Incidence e* NEQPUSTIC and NON-NEOFLAST1C
PROJECT IfrfNO: QCRESOl
MYS; flLL
GROUP;
NUMBER OF fWmiSi

KIDNEY
fiPHROPATtff, CHRONIC
1NFWH, CHRONIC-ACTIVE, PELVIS
INFUWfflCN, AOTE, PELVIS
MINERALIZAT1CN
IYMPHOCYT1C INF11TWTE
HYORONEPHROSJS
EP1TK, HfPERPLASIA, PELVIS
CYST
IWNftRY BLADDER
LWHOCYTIC INFIITIMTE
SOWKWS METAPWSIft
INFUW, CHRUUC-flCTIYE
EPHHaiAL HYPERPWS3A
INFLfltWTIlK, ACUTE
TESTES
PROSTATE
(WARY
UTESUS
EYES
WTAfWCT, LWi
IYMPHOCT. INFlLT^TE.mRD.GL
RETIWL ATROPHY
Rrrm SEGENE(WTIIIN
MTEB: ALL
SEX: FTOLE
9.WG/KG 50
20
,
It Ex 20
J
2
3
2
2
I
1
0
1 Ex 20
3
I
1
1
0
f E< 0
1 Ex «
i Ex 28
1 Ex 20
1 Ex 23
3
2 -
D
i


H6/KC
20
i
20
1
0
0
7
5
3
1
S
D
D
3
0
D
0
D
D
D
D
0
0
0
d
0
Microscopic


175HB/KS
20
i
20
3
0
D
2
4
J
0
0
23
o -
fl
0
0
1
8
a
20
20
2B
0
a
3
0
Findings


4GOH6/K6
23
„
2!
4
I
S
1
D
3
3
1
20
0
0
3
0
5
0
t
22
23
23
1
0
1)
a
CERVIX
20
23
                              (Report Continued)
                                      II-9

-------
             PATHOLOGY  ASSOCIATES,   INC.

                                 ORTHO-CRESOL
                               STUDY NO, 5221.04
                                            RATS
                   Project   Summarx  Table
    SUtWKY:  Incidenct a* NEOPWST1C and NON-NEBPLASTIC Microscopic Findings
PROJECT ID. NO: OCSESOL              FATES: ALL
              DAYS: ALL        SEX; FEM.E

GROUP:                          fl.OHQ/KO    50 KG/KG    !75ha/KS    dOOHfi/KS
NUMBER  OF (WIHftLS:                20         2D          20          23
OTHER TISSUES «D LESIONS:

(fSEMTERY-FAT NECROSIS              0          0           0
WiWft-HEHDRIWlGE,  ACi/TE            0          0           B
«AG1NHNFUW»TIDN, flWTE          J          U           0
                                  180
                                  008
                                     11-10

-------
III. TABULATED ANIMAL DATA

-------

-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                              ORTHO-CRESOl
                                           STUDY NO, 5221.06
                                          SPRA6UE-W4EY RATS
                                Tabulated  Animal   Data
                   PROJECT 10; OCRESOL     GROUP; J.OMG/KS   SEX; MALE       MYSi ALL
                   PAGE  i                 MTES; fill
         ANIMAL ID,  NO:               2891   2892   2893   2B94   2895   Zm   2897   2198   28??   290J

BRAIN                                 NNNNNNNNNN
SCIATIC mm                          N     NN     N      N     N     N      N.H      N


SPIWtf. CCRO                            NNNNNNNNNN


IONE                                  NNNNNNNNNN


mi HARIOU                            NNNNNNNNNK


SALIWRt  GLPWO                         NNNNNNNNNN
IWDIiUWR LWH NODE                   N     N            N            N     N      N
  LWHOID HYPERPWSIA                  -     -      1     -      1   '   -     -      -      1      2
THWUS                                                                      N
  HEWORRWGE, flCUTE                   (i)     W    <1)     <1)    <1>    CD    -         <1>    <2>
PftNCfiWS                               NNNNNN            NNN
  HfflOSIDEROSIS                        	<2>     -      -      -
PITUJTAiW                              NNNNNHNNNN
                                 (Report Continued)
                                                  III-l

-------
                           PATHOLOGY  ASSOCIATES,   INC

                                               ORTHO-CREBOL
                                            STUDY NO, 5221,06
                                           SPRAGUE-DAULEY  W73
                                               O
                                 Tabulated  Animal   Data
                    PROJECT ID: GCRESDl     GROUP: O.OMG/KG    SEX; MALE       DAYS: ALL
                    WSE 2                 FATES: ALL
                 ID. NO;        .        2891   28?2   28?3   2B?4   2895   2m   28?7   2898   28??   2?00

THYIOIO                                       N      N     N                          N     N
  EPITHELIAL CYST                      (35                        (3)    (1)    (1)     -     -     U?
PARATHYROID                  •          NNNNNNNNNN
TRACHEA                                NHHNNNNNNK
ESDPWQUS                              NNNHHNNNNH
                                       NKNNHNNNUN
um
  LYHPHDCYTIC INFILTIMTE.PEilV             <2>    <1>    <25    <3>        <2>
  1NFW1,  1NTESST1TWL CHRONIC          -      -      -            (1)          <2>    (15         	
HEART                                                N      N      N            N      N
  INFLATION, CHMN1C                <])    <1)                        <2)                  
-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                              QRTKO-CMSQl
                                        •   STUDY'NO,  5221.04
                                          SPRA6UE-OAULEY RATS
                                Tabulated  Animal   Data
                   PROJECT 10: OCfitSOL     GROUP;  O.OMG/KG  -  SEX; WLE       DfiYS:  ALL
                   PAGE'3                 FATES:  All
         AN1KAL ID,  HO:               2891   28?2   2B?3   2B?4   26?S   2B9i   2BJ7   2898   2B99   2?00

FORISIOWCH                            NNNHNNNNNN


GLWOUWR STWCH                      H      N     N      «'     N  '    N      N      N      N
  DIWT1CN, GUWD                      	2


SKIN              .                    HNNNNNNNNN


fWWRY 6UWD                          NUNNNHUUNN


SKELETAL MUSCLE                        NNNNNNNKNN
LIVER                                 NNNNNNN                   N
  F1IROS1S                             ....._.     (2)
        S, CWBULAT1VE                 	                  <3)
                                      N      N     N            N      N      N      H
  HEMBS1DE80SIS                        	11
  CYST                                 -      -     -     <2>    .----•--
KJWEY                                                                  N            N      N
  NEPHROPATHY, CHSflNIC                  1      1      I      -      I      -      i      -      -     2
  LYMPHOCrriC MfflLTRATE                ---
-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                              CRTHO-CRESOl
                                           STUDY NO. 5221,0$
                                          SPRAGUE-WM.EY MTS
                                Tabu!  ated  An imal .  Data
                   PROJECT ID; OCRESOL     mm?:  8.0KG/KG    SBC:  HALE       DAYS: ALL
                   PAGE 4                 FffTESi  ALL
                ID,  NO;                2891   2892   2853   2S94   29?5   Wi   2897   2890   2199   2900

TESTES                                NNNNNNNNNN
PROOTTE                               M      N                                            N
  IWHQCYTIC INFllTRftTE                -      -         <2)    (I)    <2)    (1)    <2)    -
EYES                                  HNNNNNNNNH
                                                   1II-4

-------
                                 •PATHOLOGY  ASSOCIATES,   INC.

                                                     ORTKQ-CRESOL
                                                  STUDY NO,  5221.04
                                                              MTS
                                       Tabulated  Animal  Data
                           PftOJEiH 10: OCRESOL     GROUP; O.OH6/K6    SEX; HALE      MYSi ftLl
                           PASE 5                FfflTS; ALL
                        ID.  NO;              2891   2892   23?3   2S94   23J5  28?5  2897   2898   1899   2900

OTHER TISSUES (5ND LESIWS;

         MESENTER1C LN-HEMOfiR»GE               	2      -
         ING. LH-LWHOID HtPERPWSW           	2
                                        (Report Continued)
                                                         III-5

-------
                          PATHOLOGY  ASSOCIATES,   INC

                                             ORTHSHRESOL
                                          STUDY NO, 5221.Hi
                                         SPRAGUE-EtfULF?  RATS
                               Tabulated  Animal   Data
                   PROJECT  ]D: CCRESDL     GROUP: Q.OHG/KS    SEX:  Wit       DAYS! ALL
                   PflGE 6                FATES: All
         (MWd ID, NO;               2901   2902   2903   29fl4   2905   2901   29(17   2?J8   2909   29!9

                                     NNNNNNNN'NN


SCIATIC NHNE                         NNNNNNNNNH


      CORD                           NNNNNNNNNN
8DNE                                 NNNNNNNNNH
                             o

mi mm                           NNNNNNNN.NN
SALIW1Y 6UWD                •        NNNNNNNNN'"N
HOT! KJLAR LYMPH NODE                               N           N                  H     N      H
  LWHOID HYPERPLASW                 22-2-22---
WfflUS                                                         N      N                 N
  HEMflRRWOE, ACUTE                   <2>    <2)    (1)    (»    -      -    <1>    U3    -     (1)
WWCREAS                                    N      N     N            N           N      N      N
  H9WSIDEROSIS                                                 <1)
  INFUWttTlffl, CHROKIC-^aWE          ,-._..    (2)
  AC3NAR ATROPHY                      <1)    -.,-.-
PITUITARY                             N     N      UN     N      N     N     N~N      H
                                (Rspari Continued)
                                                  111-6

-------
                           PATHOLOGY   ASSOCIATES,   INC.

                                               OffTHfl-CRESQL
                                             STUDY NO, 5221.U
                                            SPRAGUE-DAULEY MS
                                 Tabulated  Animal   Data
                    PROJECT Id OCRESQL     GROUP: Q.OKG/KG    SEX:  Mil       DAYS; ALL
                    PAGE ?                  FATESi ALL
               i  ID, NO:                2901    2902   2903   2904   2J05   2904   2907   2M8   2909   2910

THYROID                                 N             N            N                   N      N
  EPITHELIAL CYST                        -      <1)     -     (1)     -     <2>    <2>    -      -     <2>
  LYMPHOCYTE INFILTRATE                 ...     ^     ......
PARATHYROID                             UNKNNNHNMH
                                        NNNNN             NN'NN
  LYltfHOCYTIC INFILTMTE                 	<2>
ESOPmGUS                              NNNNNNNNNN
        6LAND                                 N      N            N      N            N      N
  ECTASW,  MEDULLA                       1      -      -      i     -      -      2     -      -      1
LUNS                                                                                         N
  LYHPKOCYT1C  INFILTRATE,PERiy          <2>     <3)    (2)        <2)    <2)     -      -
  1NFLAH,  INTERSTITIAL CHRCNIC          (1)     (25     -      -         <2)           (1)
  HISTICCYTOS5S                          -      -     (1>     -      -     <1)     -      -      -
  PNEU1CNIA, FORllffl BODY                	(2)
HEART                                                       N     N      N      N            N
  INFLATION, CHRONIC                 (!)    <1)    (2>     -     -      -      -     <2)     -     <1)
AORTA                                  NNHNNHNNNN


COLON                                  NNNNNNNNNN
                                  (Report  Continuidl
                                                     III-7

-------
        PATHOLOGY  ASSOCIATES,   INC.

                            QRTHO-CRESOL
                         STUDY NO. 5221.04
                                      RATS
             Tabulated  Animal   Data
PROJECT  ID; OCRESOL     GROUP; O.OH5/K6    SEX: WLE       DAYS; ALL
PAGE 8                 FATES: All
DUflDENIH
                ID, NO:
                   2901    29D2   2903   2904   2905   2?U   2m   2908   290f   2915

                    NNNNNNNNNN
FORESTOWCH
                    NNNNNNNNNN
GUNDUWI STOMACH
                    NNNNNNNNNN
SKIN
                    NNNNNNNNNN
                    NNNUNNNNNN
SKELETAL MUSCLE
                    NNNNNKNNNN
LIVER
  INFWMftTIDN, CHRONIC
                                       N     N      N      N     N
                                                                  N     N
SPLE0<
  HEMOS1DEROSJS
                                                                  N     N
                    1      2      1      1      2      1      2      -     -      1
KIDNEY
  NEPHROPffTW, CHRONIC
  LYUPHflCYTIC INFILTRATE
                          N      N     N      N
                    1      -      -     -      -      1       2      1
                                                                        <1>
URINARY  BLADDER
  CALCULUS
                    N            N                   N     N          -  N      N
                          I      -      2      2      -     -      2
              (Report  Continued)
                                 II1-8

-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                               ORTHO-CRESOL
                                           STUDY NO, 5221,04
                                           SPRAGUE-MULFY RATS
                                Tabulated  Animal   Data
                   PROJECT  ID: OCRESOL     GROUP; O.OMS/K3    SH; MALE       MYS:
                   PAGE  ?                  FATES: ALL
                ID, NO;                ini   2902   2?03    2?04   2905   29U   2907   2?08  2?09   2918

TISIES              '                   NNNNN            MHHH
  ATROPKf, SEMINIFEROUS TUBULE           	     <1>
PROSTATE                                      N      H     N             H             N            N
  LYWPHOCYTIC INFILTMTE                <2)                        <1>     -          -    <2>
EYES                                   NNHNNNNHNH
                                 
-------
                                    PATHOLOGY  ASSOCIATES,   INC.

                                                       QRTHQ-CRESQL "
                                                    STUOY NO, 5221,06
                                                    SPRAGUE-MULEY WTS
                                         Tabulated  Animal   Data
                            PROJECT ID: OCRESDL     GROUP; fl.DHG/KG   SEX: HALE       MYSr ALL
                            PAGE 10                FATES: ALL
                          10, NO:               2901   2W   2?03   2?D4   2f05   21U   2W   l?m   2?0?   2910

OTHER TISSUES m LESIONS!
                                          (End 
-------
                          PATHOLOGY  ASSOCIATES,   INC
                                          STUDY NO. 5221. Oi
                                         SPiWSUE-MWLET RATS
                               Tabulated  Animal   Data
                   PROJECT 10; OCRESCL    GROUP: fl.OMS/KC    SEX: FEWLE     DAYS: ALL
                   PAGE 1                FATES: ALL
         ANIfttL ID. NO;               3023   3U24   3025   302S   3827   3J28   302?   3033   303!   3032

8M1N                                 NNNNNNNNNN


SCIATIC NERUE                          NNNNNNHNNN


&1WL CORD   •                         NNNNNNNNNN


BONE                                  NNNNNNNNNN


SON! mm                            NNNNNNNNNN


SAL1MAKY GLAND                         NNNNNNNNNN
KWBIJLAR LWH NODE                                            N                  N
  LWPHUID HYPERPLASIA                  1311-13-22
THYMUS      ,                          N      N           N                  N
  HMRRWSE, ACUTE                    -                     
-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                              ORTHO-CRESOL
                                           STUDY NO.  5221.U
                                           SPRftSUE-WLET WTS
                                Tabulated  Animal   Data
                   ADJECT  ID: CCRESOL    GROUP: O.WG/KG    SEXi  FEWIE   '  DAYS: ALL
                   PAGE 2                FATEi: ALL
         ANIHAL ID. NO:                3023   3(124   3025   3026   3327   3028   3029   3Q35   303!   3032
                                                                        &
THYROID                                                   N     N                                N
  EPITHELIAL CYST                      (2)    (1)    (1)     -     -     <2>    <2)    (J)    <2>
WRATKYROID                             NNNUIJHUHNN
TfWCHEA                               N            NNNNNNN
  LYMPHOCYTIC INF1LTEATE                      <1) •	(1)
ESOPHAGUS                              NNNUNNNNNN


                                      NNNNNNNN            N
  ECTASW, HEDULLA
IONS
  LYMPHQCYT1C !NF!LTt»TE,PERiy          (1)    «>    <1)    <2>    <2)    
  INFLrtl,  INTERSTITM CHRONIC           -      -     <1>    
-------
        PATHOLOGY  ASSOCIATES,   INC.

                           ORTHO-CRESOL
                     •   STUDY  NO. 5221,06
                       SPWGUE-MULEY MTS
             Tabulated  Animal  Data,
PROJECT  ID: OCRESOL     GROUP;  O.DHG/KS    SEX: FEMALE    DAYS; ALL
PACE 3     ,            FATES;  ALL
         ANIMAL 10, NO:
DUODENUM
                  3023   3024   3025   302i   '3C27   302S   3029   3030   3031   3032

                   NNNNNNNNNN
F08ESTONACH   '
  CDNBEST10N
                   N.NNNNNNN            H
                   ........      2     -
6WWDUWR STffttCH
                   NNNNNNNNNN
SKIN
                   NNNNNH.     NNNN
        GUftD
                   NNNNNNNNNN
SKO.E1AL H'JSCLE
                   NNNNHH-HNNH
LIVER
  INFWtWTICN, CHRONIC
                   NNNH.NNN            N
                   .......     <1>     -    W
SPLEEN
  HEHDS3DEROSIS
                   NNNN
                                             2  '    2      2     2      2
KJWEY
  INFIAK.CHRDNIC-ACTWS.PEWIS
  MINERALIZATICN
  LYHPHOOTIC JNFILTIWT!
                                                   N     N      N            N     N
                                                                      (2)     -     -

                                                                      <2>     -     -
                                                                      U)
              < Report Con tinned)
                                111-13

-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                              ORTHO-CRISOL
                                           STUDY NO, 5221,06
                                          SPRAGUE-DAULEY RATS
                                Tabulated  Animal   Data
                   PROJECT IE): OCSESOL     SROyP;  fl.OHS/KO    SEX: FEmiE     DftYS: ALL
                   PftGE  4                 FATES;  AIL
                ID,  NO:               3023   3024   3025   3024   3827   3028   3029   3030   3Q31   3032

        8LADOER                               NNNNNNNN
  LYHPHDCYT1C INFILTRATE               <1>           -      -	(1)
(WRY                                 NNNNNNNNNN


IfTilUS                                 NNNNNNNNNN


RES                                         NNNNNNNHN
  LWHOCY. 1NF1LTMT£,»RD,GL         (2)           	


CERVIX                                 NNNNNNHNNN
                                 (Report Coatinutd)
                                                   111-14

-------
                                  PATHOLOGY  ASSOCIATES,   INC

                                                    OmiQ-CRESQL
                                                 STUDY NO. 5221,W
                                                 SPRAGUE-WW.EY RATS
                                       Tabulated Animal   Data
                           PROJECT ID; DCRESOL     SRQUP: 0,TO/KG   SEX; FEmiE    MYSi ALL
                           PAGE 5                FATES; ALL
                        JO. NO;              3D23  3024  3025   3024   3027   3028   3fl2?   3030   303!   3i32

ffTHER TISSUES AND LESHNSs
                                        
-------
                          PATHOLOOY  ASSOCIATES,   INC.

                                            ORTHQ-CRESOl
                                         STUDY NO,  5221.04
                                                      RATS
                               Tabulated  Animal  Data
                   PROJECT  ID; OCRESOL     SROUPs O.OHG/KS    SEX; FEWLE     MYS; ALL
                   PAGE 4                 FATES; AU.
                10. NO:              3(133  3034   3035   1036   3D37  3038   3039   3040   3041    3042

BRAIN                                NNNNNNNNNN


SCIATIC NERVE                         NNNNNHNNNN
      CORD                           NNNNNHNHHN


BONE                                 N'NNNNNNNNN


KM mmw                           NNNNNNNNNN


SAL2MARY flWD                        HNNNNNNNNN
          LWPH NODE                  N           N     N                  N      N     N
  LYUPHDltt HYPgRPWSlft                       3     -     -      1     I     -      ~     •     i
"WfflUS                                                         N     N     N
  HBWRRHA6E, ACUTE                   <2>    (1)    (2>    «>                       (1)
mmm                •              NNN            NHNNNN
  IYWHCCYT3C INFILTRATE                                  <»	
PITUITARY                             NNNHNNNNNN
                               (Report Continued)
                                                 111-16

-------
        PATHOLOGY ASSOCIATES,   INC

                          OTM-CRESOL
                        STUDY NO. 5221,06
                       SPMGUE-MUIEY  RATS
             Tabulated  Animal   Data
PROJECT ID; QCSESOL     GROUP: O.OHG/KG    SEX; FBtfLE     DAYS: ALL
WGE  ?                 FATES; ALL
              i ID. NO:
TlffSJIO
  EPITHELIAL C7ST
                  3(133   3034   3D35   3034   303?   3038  303?   3040   30«   3fl«

                                            N            N      N      N
                                     (1)     1     <2>    <2)
                                                                            (1!
PARATHYROID
                                      IINNNN
                                                         NNNN
TRACHEA
  LYHPHOCYTIC 1NFILTMTE
                                            N            N     N
                                                  
                                                         N      N      N     N
                   NUNNNNNNNN
(WML 6UWD
  ECTASW, MEDULLA
                   NN^NH            NN            NK
                                             1      -     -      1
LlTiG
  LWHOCYTIC
  IMFW1, INTERSTITIAL CHRtNIC
  HJSTiOCYTOSIS
                                     (2)
                                                              <2>
                                                        U>    <»
                                                               (1)
                                                                     <2>
«»RT
             ,  CHRONIC
                   NNN           NNNNNN
                   ---    .....
AORTA
                   NNNNNNNNNN
COLON
                   N     N      N     N     N      N     N      N.N     N
             (Report Cantinusd)
                               111-17

-------
        PATHOLOGY  ASSOCIATES,   INC.

                           OSTHO-CRESOL
                        STUDY NO.  5221, U
                        SPRAGUE-MULEY »TS
             Tabulated  Animal   Data
PROJECT  10: OCREBCL     GROUP: 0.OHO/KG    BEX: FB4H.E     DAYS: ALL
PftGI  8                  FATES; AIL
OUODWUN
                10. NO:
                   3033   3034   3035   3031   3837   3038   3039   3040   3041    3042

                   NNNNNNNNNN
  CONGESTION
                   NN'NNNNN            NN
                   .......     t      .     .
          STQtttCH
                   NNNNNNNNNN
SKIN
                   NNNNNHNNNN
HWIWRf  SL««
                   NNNNNNNNNN
SKELETflL MUSCLE
                   NNNNNNNNNN
IMR
  INFLrttttTIDN, CHRONIC
  UP1DOSIS
                                N      N
                                                   
-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                               ORTHO-CRESOL
                                            STUDY NO, 522144
                                           SPRA6UE-DAULEY RATS
                                Tabulated  Animal  Data
                   PROJECT ID; OCRESOL     flRQUP; 0.0H6/KG    SEX: FEMALE     MYSi ALL
                   PAGE 9                 MTES: ALL
                 ID, MO:               3033   3034   3035   3034   3037   3038    3039   3040   30-11   3042

KIDNEY                     •-           H     N                   N      N            N     N      N
  NEPHRWWHY,  CHRONIC                  ......     |      ...
  N1NEWLIZATIOH                        -------
  saumous METAPLASJA                   	cz)     -     -      -
  1NFLAM, CHRCNIC-ACTIVE                	2      -     -      -
  EPITHELIAL HYPERPWSJA                	W
WRY                                 NNHNNNNNNN


UTERUS                                NN-NNNNNNNN
EYES                                         NHNNNNN            N
  LYHWOCY. INFILTMTi,HARD,6L           	CD     -
         DESENERATIDN                  2	-      -
                                      NNNNNNNNHN
                                 (Report Continud)
                                                   111-19

-------
                                   PATHOLOGY   ASSOCIATES,   INC.

                                                      ORTHQ-CRESOL
                                                    STUDY NO, 5221.0(5
                                         Tabulated  Animal   Data
                            PROJECT IDs QCRESOL     GROUP: fl.OHG/KS    SEX: FEMALE     WYSs All
                            PftGE  10                WTESi ALL
                         ID.  NO;               3033   3034   3835  3034   JI37   3038   303?   3040   3041   3042

mm TISSUES 
-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                             DRTKO-CRESOL
                                          STUDY NO, 5221.J4
                                         SPW6UE-W4EY  WTS
                               Tabulated  Animal   Data
                  PROJECT  ID; OCRESOL     GROUP: 50 H5.K5    SEX: WLE       DAYS: AU.
                  WBE i                 FATES; ALL
                ID. NO:              2924   2925   2m  2927   2928   2929   2930   2931   2932   2933

BRAIN                                *      *      *     *      »      »     *     *      *      »


SCIATIC NERVE                         i      «      »     «      *      *     *     f      §      i


SPJWL CORD                           *      «      *     *      *      f.»     i      i      I
80NEWRRBU                     .      i      i      »     «      «      i     »     »      i     i


SkLJWRY GU«0                        i      i      f     i      *      i     i     I      «     «


NWDJBULAR LYMPH NODE .                 *      *      *     f      *      *     *     *      »     »


THWUS                                «      *      *     *      •      *     «     *      *     «


fWCRWS                              «     ' *      *     *      f'»     •     *      i     i


PITUITARY   •                          i      i      f     »      i      *     i     §      i     «


THYROID                               **»iiiiJ*.i


WRATHYROID                           *      *      •     *      *      *     *     *      *     *
                                
-------
                         PATHOLOGY  ASSOCIATES,   INC.

                                            OffTHQ-CRESOl
                                         STUDY NO, 5221,0<
                                        SPMGUE-WJtiY  RATS
                              Tabulated  Animal   Data
                  PROJECT ID;  (JCRESOL    GROUP!  50 HE,KG   SEX; fttlE       WYS: ALL
                  PASS  2                FATES;  All
ID. NO;
                                          2?25   2?24

                                     *     *     *
                                                             2?28   2?2?   2?30   2?3J    2932   2?33

                                                              *      »      *     * '    *      i
ISOPWfiUS
                                     ttttittttt
mmi
                                     *      »     *     *      *      »     *     *     »      «
LUNG


HEART


AORTA
                                     »      »
                                     »      i
                                                              *      *      *
                                                                                      *      *
                                                       i      •      i     »     i '    i      i
COLON


9UODENU1


FDRESTOWCH


SWHOULAR STOMACH


SKIN


       6WNO
                                     iii»*i*i*'t
                                     *      *     *     *      »      »*
                                     ttttttiit*
                                     *      i
                                                       i      i
                                                                          »     i
                                     Itilililt*
                                     *      »     •
                                                              i      »     *
                               (Report Continued)
                                                 111-22

-------
                           PATHOLOGY  ASSOCIATES,   INC

                                              ORTHO-CRESOl
                                           STUDY NO,  522! ,0d
                                          SP!WGUt-!MLEY  SATS
                                Tabulated  Animal   Data
                   PROJECT ID; OCRESUL     GROUP: SO  HG.KG    SEX; WLE      »YS; ALL
                   WGI  3                 FATES: ALL
                ID. KOi                2924   2925   2m   2927   2928    292?   2?30    2931   2?32   2933

SKELCTflL MUSCLE                         *»*ii*i*ii


IMR                                  i*iiii»iii
KiCNEY                                N                                       N
  NEPHROMTHY, CHRONIC                                            1       i      -     i      1
  LYMPHOCYTE 1NFILTWTE       -        -     (I)        CD	
  HYORCNEPHROSIS                       	(2)
UR1WRY ILflOOER
TISTE3                                 *      *      *     »      *      *            *t*
  ATROPHY,  SEMINIFEROUS TUBULE           	     131
  HYPEWWSJA, MERSTIT,  CRL           	<2)    -      -     -
PROSTATE                               *      *      «      »      *     <*      *


EYES                            .       i      i      *      i      »      i      »
                                 (Report  Contisuid}
                                                   111-23

-------
                                    PATHOLOGY  ASSOCIATES,   INC

                                                        ORTBO-CRESOL
                                                    STUDY NO. 5221,01
                                                    SPftGUE-MULSY RATS
                                         Tabulated  Animal   Data
                            PSOJECT ID: QCRESQL     GROUP: 50 HG.K6    SEX; fWLE       MYS;
                            PAGE 4                 FATES: AIL
                          ID. NO!               2924   2925   2?24   2?27   2921   2929   293Q   2931    2932   2933

OTHER TISSUES (W LES1INS;
                                          (Report  Continued)
                                                             111-24

-------
                          PATHOLOGY  ASSOCIATES,   INC,

                                             ORTKC-CRESOL
                                          STUDY NO. 5221,OJ
                                         SPMGUE-WULEY RATS
                               Tabulated  Animal   Data
                   PROJECT ID; OCRESOL     SROUPi 50 HB.KS   SEX: WL£       WYSi ALL
                   PAGE 5                FATES; ftll
         ANNWL ID. NQ;               2534   2935   293i   2937   2933   273?   2940   2941   2?42

                                      i      «      i     »      i     i      i      *      i     i


SCIATIC NERUE                          »      I      •     *      »     1      *      *      »     *


      CORD                            tiittitttt


                                      *      i      i     t      i     *      i      *      »     i


SINE IWJROU                            ii**«*-tiji


S5LIWRY 5UWD                         fiiit*t'i*i


(WDI8UWR LYMPH NODE                   i      *      *     *      *     *      *      «      »     «


THTMUS                                 »      *      *     »      *     *      *      '      *     *


WWCRIAS                               i      »      t     f      *     i      *      i      J     »


PITUITARY                              *      *      *     »      *     *      *      «      *     »


THYROID                                »      »      »     *      »     «      »      »      *     *


MftttHYROIQ                            »      »      i     »      *     *      *      *      *     *
                                (Report Continued)
                                                 111-25

-------
                          PATHOLOGY  ASSOCIATES, .INC

                                             ORTHQ-CRESOL
                                          STUDY NO, 5221.04
                                         SPMGUE-MULEY fWTS
                               Tabulated  Animal   Data
                   PROJECT ID; OCRESOL    SROUP:  SO HB.K6    SEX: MALE      WYS: ALL
                   PAGE &                FffTES:  AH
                ID. NO;               2934   2935   2934   2937   2938   293?   2940   2941   2942   2943

TRACHW                                ii»j»»i*ii


ESOPWGUS                              »      *     i      t     *      i      i     i      *      t


ADRENAL 6LWD                          »      *     *      *     *      *      *     *      «      *


LING                                  1      t     i      *     *'i      I     I      i      *


HEART                                  titttttttt
DUODENUM                              ii«*i*tfi*
FQRESTfftfCH
SUWOUWR STH«C«                      i      *     »      *      *      i      »     »      *      *
SKIN                                  ltiifi*»ii
       SUW                         i      i      i      *      *     I      i     i      t      *
                                (Report Continued)
                                                  111-26

-------
                           PATHOLOGY  ASSOCIATES,   INC,

                                               ORTMKRESQl
                                            STUDY NO. 5221,04
                                           SPRACUE-OAULEY RATS
                                Tabulated  Animal   Data
                   PRWECT ID;  QCRESOL     6RCUP;  50 MS.K8    SEX: mil       MYS; ALL
                   PAGE ?    '             FATES: All
          ANIMAL 10. NO:               2934   2?35   2?3i   2937   2?38   2939   im   2941   2?42   2543

SKELETAL MUSCLE                         »      »      *      »      *      »      »      «      I     «


LIVER                                  iiifii*»*i


SPLEEN                                 Jiiitiifii
KIDNEY
  NEPHRQMTHY, CHSflNIC                               1      1       I
              , ACUTE, PELVIS           <1)
URIWRY 8WDOER                         i*ifiii*i»
TESTES
PROSTATE               •                 i**i*itti*
                                       *      »      *     , *     *      «      »      *      *     *
UliRUS                                 *     *      *      *     *    •  *      *      t      i     *
EYES                                   liiiiii**»
CERVIX                                 l      *      »      *     *      *      *      t      »     *
                                 (Report  Continued)
                                                    111-27

-------
                                    PATHOLOGY  ASSOCIATES,   INC.
                                                        ORTHO-CRESOL
                                                     STUDY NO, 5221.04
                                                    SPRAGUE-M4EY MIS
                                         Tabulated  Animal   Data
                            PROJECT ID;  QCRESOl     GROUP; 50 KG,KG    SEXs fttlE       MYS; ftll
                            FACE 8                 FATES: All
                          ID. NO:               2934   2935   2?36   2?3?   2938   293?   2930   29«   ZJ«   2J43

OTHER  TISSUES AND LESICNSs
                                          (End »f Report)
                                                             111-28

-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                              ORTHO-CHBOi
                                            STUDY NO, 5221.06
                                           S?RAGyE-MULEY RATS
                                Tabulated  Animal   Data
                   PROJECT ID;  OCRESOL     6RQUP; 50 MS/KS   SEX: FEfttLE    DAYS; ALL
                   MGE i                 FATES: All
                 ID, NO:               305(5  3857   3058   3059   3040   mi   3042   3043   30*4   3045
SCJflTIC NERVE                           i      *      •     *      *      i      i      i      »      i


SPimL CORD                            i      i      i     i      i      i      i      i      «      I


BONE                                   iii»«if!'»i


BONE IViRRDU              ^              ii^intiiiit


5ALIWRY SlJiNO                          »      «      »     *      i      »      t      f      i      i


MW01BULAR  LYMPH NODE                   I      i •     i     i      i      i      i      i      i      i


THYMUS                                 i      i      *     •      t      *      *      »      *      *


fWCREAS                               i      i      t     i      i      i      4      E      i      i
TKYROJD                                II      i      1      i      i      i     i      i     i
PARATWR010                            *      »      *      t      *      »      i     *      *     *
                                 CReport Continyid)


                                                   111-29

-------
        PATHOLOGY  ASSOCIATES,   INC.

                           QRTHO-CREStt
                        STUDY NO, 3221.06
                       SPRdBOE-MULEY RATS
             Tabulated  Animal   Data
PROJECT  IB: BCRESOl     8ROUP:  50 HG/K6    SEX: FEfttLE     DAYS; ALL
PAGE 2                 FflTES:  All
TRACHEA


ESCPWGUS
                ID. HO:
LJNG


HEART


AORTA


COLON


OUODENUH


FORESTttfcCH


BWNOULAR STOMACH


SKIN


       GLAND
                  3056   3057   3(158   3059   3J3iO   3041   3042   3043   30«   304S

                    I      i     *      j     *      t      »      i      i      i


                    *i«i«iii*i


                    »      »     «      *     *      *      i      i      i      i


                    *      *     *      >     *      *      i,i      i      *


                    i      t     i      «     «      i'     i      i      «      i


                    fi***t*t»*


                    liitiitlii


                    ii»>iiti»<


                    itiiitttii


                    I      •     *      *     »      t      «      t      *      *
                   i      »      i      i      i
                                                          »      i
                   i*iif*»iii
              (Report Continuid)
                                111-30

-------
                           PATHOLOGY  ASSOCIATES,  INC.

                                               ORTHO-CRESDL
                                           STUDY NO, 5221.Oi
                                           SPRAGlie-BAULEY RATS
                                Tabulated  Animal   Data
                   PROJECT 10: QCRESOL     GROUP: 50 ME/KB    SEX; FEHALE     MYSi ALL
                        3                 FATES! ALL
                ID, NO;
SKELETAL MUSCLE
LWER
                                      3J5^    3057   3058   3J5?   3640   3041   2Q62   3023   3064   3045
KIDNEY
  «PHROPftTHY, CHRONIC
  HINEJMLIMTKW
  LWHOCmC INFILTiWTE
  iffDRIWEPHROSIS
  EP3TH, ffifPERPLASIA, PELVIS
(1)
                                                                (13
                                                                                                  i
                                                                                                 (1)
                                                                                           (»
        BUDDEH
UTERUS
                                                                                     »     *      *
EYES
                                       ii»**ttit*
CE1W1X
                                                    §     *
                                 (Report
                                                   111-31

-------
                                    PATHOLOGY  ASSOCIATES,   INC

                                                        ORTHO-CRESDL
                                                     STUDY NO, 5221,04
                                                    SPMGUE-MM.EY ftVFS
                                         Tabulated  Animal   Data
                            PROJECT ID:  OCSESQl     GROUP: 50 N6/KS    SEX: FEWLE     MYS: ALL
                            WGE 4                 FATES: ALL
                          ID. NO:               3m   3057   3058   3flS?   30<50   30«1   30
-------
                          PATHOLOGY  ASSOCIATES,  INC

                                            smo-CREsoi
                                         STUDY NO. 5221.04
                                        SPW5K-MULEY  RATS
                               Tabulated  Animal   Data
                  PROJECT  ID: OCRESQL    GROUP;  50 HG/KS    SEX:  FEmii    MYS; ALL
                  mi 5                FATESs  ALL
         ANIHfll ID. NO:               3B44   3047   3048  304?  3370   307!   3072   3073   3fl74   3075

 BRAIN                                **«»*iiiii


 SCIATIC NSWE                         *      *     *     *     t     i      *      *     I     »


 SPINftl CORO                           *      f     i     I     i     *      »      I     i     i
SINE MftRRDU                           *      t      i     i     t     t      i      »
IWDIBIIWR LfflPH NODE                 ittittttit


TtffflUS                               i**lit!t»!



WNCREftS                             iifi«fi«»f



PITUITflRY                        '*      i      *      *.»     t     »      i      t     i
WRATWROIO
                               (Report Continued)
                                                111-33

-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                              ORTKO-CRESOL
                                           STUDY NO. 5221.04
                                          SPIW61E-MULEY RATS
                                Tabulated  Animal  Data
                   PROJECT ID: OCRESOL     GROUP:  50 HE/KG    SEX: FttMLE     DAYS: ALL
                   W6E I                 FATES:  ALL
                10.  NO:               3844   304?   3040   384?   3070   3071   3G72   3073   3Q74   3075

TRACHtt                               I      i      i      I      *      i      i      i      i      f


ESOPHAGUS                              *      *      *      *      *      »      *      *      *      i


A0RBWL 61JND                          i      f      i      i      i      i      «      i      i      *
HEART
COLON                                 fill*      iti      ii


DUQOEMH                               *ii»**i*i§


FORiSTtMACH                            i      i      «      I      »      *     I      I      i      *


6UWULAR STQWCH                      *      *      *      *      *      *     *      »      »      »


SKIN                                  i      i      «      i      I      I     t      i      i      »


       ELM)                          *»ti*t»i#*
                                 (Reaort Coniinued)
                                                  111-34

-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                              OTO-CRtSOL
                                           mm NO, 3221.04
                                          SPRftGUE-DAULEY RATS
                                Tabulated  Animal   Data
                   PROJECT  ID: OCRESQL     5ROUP;  50 H6/KS    SEX; FEWLE     DAYS; ALL
                   PAGE 7                 FflTES: ALL
                ID, NO:               3064   3067   3fla3   3049   3070   3071   3072   3073   3D74   397S

SKELETAL MUSCLE                        *      *     «      *     i      *     *      *     *      «
SPLEEN                                *iiiiiiiii
KIDNEY                                       N                  M      N     H      N     N
  NEPHSOPATHf, CHRONIC                              1      -------
  MINERALIZATION                      <2)     -     -     <13     -      -     -      -     -     -
  LWHOCYI1C INFILTI^TE                                   <1)	<3>
  HYORONEPHi?OSlS                       1	-
mimm ILAOOER                    .iijiiiiiii


TEfTES                                i*iii«,i»i»


PROSTATE                              §      i      i      i      j      «     i      i      I      i


(WARY                                 »      §      »      *      *      *     *      i      i      i


UTERUS                                *      »      *      »      *      *     *      *      »      *


EYES                                  »      *      »      »      t      i     ii,»*
                                        Continued)
                                                   111-35

-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                             HTHO-CRESDL
                                          STUDY NO. 5221,01
                                                       ftvrs
                               Tabulated  Animal   Data
                   PROJECT ID: OCSBOL    S80UP:  50 MS/KS    SEX:  FBttLE     DAYS! AIL
                   PAGE 9                FATES:  ALL
                10. NO;               3J«   33^7  30^8   30^?  31170   3fl71   3072   3073   3074   3i?5

CERVIX                                 t     't     t      i     i      i      i      i      *     i
                                (Report Continued!
                                                 111-36

-------
                                PATHOLOGY  ASSOCIATES,   INC.

                                                  OOTHO-CRESOL
                                               STUDY NO. 3221.04
                                               SPMGUE-DAyLEY MTS
                                     Tabulated  Animal   Data
                         PROJECT ID:  OC1ESOL     GROUP:  50 HSXKG    SEX; FWLE    DAYS; All
                         MGE ?                FATES!  ALL
                 mmi ID. NO;             m&  mi   im   iw   mn   2071   3072   2073  2074  3075

OTHER TISSUES (WD LESIONS;
                                      (End tf Report)
                                                      111-37

-------
                           PATHOLOGY  ASSOCIATES,   ]NC.

                                               QRTHO-CRESOL
                                            STUDY-NO, 5221.Oi
                                           SPRAGUE-WJLEY RATS
                                 Tabulated  Animal  Data
                           ID; DCRESOL     GROUP: 175NG/KS    SEX: fMLE       DAYS; ALL
                   PftGE 1                 FATES: ALL
                 ID. NO:                2757   2958   2939    29    <2)    <1>     <1)    <1>     -    <2>    <2>    (1)
MNCi?EAS                               NN            NK            NNNN
  LYHPHOCYTIC  INFILTRATE                -      -     (1)     -
               CHRONIC-ACTIVE          .....     <1)            -   .--  -
PITUlTAITf                               NNNHNNNNN'N
                                  (Report Continued)
                                                    111-38

-------
                           PATHOLOGY  ASSOCIATES,   INC.

                                              (FTHQ-CRESOl
                                           STUDY NO.  5221,04
                                                         RATS
                                Tabulated  Animal   Data
                   PROJECT  ID: OCRESOL     GROUP; 175HB/KG    SEX: fttLE       MYS; ALL
                   PAGE 2                  FATES: ALL
          ANIMAL ID, NO:                2?57   2?5B   2?5?   2960   2961   2942   2?d3   29«   2945  2?6i

WYRQIO                               N      N      N
  EPITHELIAL  CYST                      -             -     (2)    (1)    (1)       .<1)    (1!
MRflTHYROlD                            NNNNNNNNNN
TRACHEA                               N      N     N      N      N            N     N      N     N
  DILATION,  6LANDS        .             	<2>
ESOPlttGUS                             NNNNNNNNNN
»R£NAL 8lJ«0                          H            N             N     H      N            M  -   N
  ECTASIA, HEDULW                            2     -      2      -     -      -     2
LUN6
  LTHPHOcmc !NFIL™TE,FERIV                  <2>                <2>    o>     (2)
  1NFLW,  IMTERSTJTWL  CHRONIC          -      -     (1)    U>     -     -      -    <2>    (2)     <1)
  OSSEOUS  HEWUSIft                   	    -     <1)     -     -     <2)    <1>    <3)


AORTA                                 NNNNNNNNNN


COLON                                 N      N     H      N      N     N      N     N      N     N
                                 (Report Continued)
                                                   111-39

-------
PATHOLOGY  ASSOCIATES,   INC.

                    (RTBQ-CRESQl
                 STUDY NO, 5221.04
                SPJWGUE-IMUIE? RATS
      Tabulated  Animal   Data
                    PROJECT 10; OCRESOL     SRQOP:  17S1G/KG    S£Xi  MALE
                    PrtCE 3                  FATES: fill
                                                 DAYS:  ALL
HJOOEN*
                 ID. NO:
           2957   2?58   295?   29dO   2?61   29d2   29(53   2964   2945   2U&

            NNNNNNNNNN
FORESTQWCH
            NNNNNNNNNN
            NNNNNNNNNN
SKIN
            NNNNNNNNNN
NftMfcRY
                                       NNUNNNN
                                                                  NN
SKELETAL MUSCLE
            NNNNNNNNNN
LMR
  IMFARCT,  CAUDATE LDIE
  LYMPHOCYTIC  INFILTRATE
            N       .NNNNNNN
            -   •   4
                                                                        <1)
  HEMOSIDEROSIS
            NMNNNNNH
                                                                  11
MONEY
  NEPHROPATHY, CHiDNIC
  LYHPHOCYT1C  INFILTRATE
                                        -1-21
                                       <$>     -     (1)     -      -
                                                     2111
       (Report Continued)
                         III-40

-------
                          PATHOLOQY  ASSOCIATES,   INC.

                                              GRTHD-CRESOL
                                          STUOY MO, 5221.Oi
                                          SPWGUE-MULFY WTS
                                Tabulated  Animal   Data
                   PROJECT ID:  OCRESOL     GROUP; 1?    <2)    (3)     -      -     -     <1)    <2>    
-------
                                   PATHOLOGY  ASSOCIATES,   INC,

                                                      fliTHC-CRISCL
                                                   STUOY NO. 5221,04
                                                                WTS
                                        Tabulated  Animal  Data
                           PROJECT IDs OCRESOL    SROUP;  175K6/K6    SEX; 1*L£      DAYS; AH
                           PAK 5                FATES:  ALL
                  flUNW. ID. NO;               2557   2?58   2959   29iO   29^1   2?42   2943

UTHER TISSUES WO LESKWSi
                                         (Report
                                                           111-42

-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                             8TO-CRESOL
                                          STUDY NO, 522S,Oi$
                                        , SPRAGUE-MULEY RATS
                               Tabulated  Animal   Data
                   PROJECT 10i QCRESOL    GROUP:  175HG/K6    SEX; mil       DAYS; ALL
                   PAGE 4                FATES;  ALL.
                ID. NO;               IW   29W  2919   2J78   2?7!   2572   2973   2974   2975   2976

BRAIN                                HNNNNNNNNN


SCIATIC NERVE        •                 NNNNNNNNNM


mm. cosa)                           NNMNNNNNNN


iONE                                 NNNNNNNNMH


BONE mRftOU                           NNNNNHNHNN
        SWND                        NNNN'NNNNN
  LYHPHOCYT3C INFILTRATE               ,....,...
          LtHPH NOOi                      '               N      N     N     N                  H
  LYMPHOID KYPERPLAS1A                  23J----I2-
THYHUS                                                         N           N
  B10RRKA5E, flCUTE                    <1)    (I)    (!)    
-------
                         PATHOLOGY  ASSOCIATES,   INC.

                                           ORTHO-CRESOL
                                        STOY NO, 522J.06
                                       SPfWGUE-WJLEY SATS
                              Tabulated  Animal   Data
                  PROJECT ID; QCRESOL     GROUP:  1731S/KS   SEX: WLE      CAYS: ALL
                  »G£ ?                FATES:  ALL
         mmi ID, NO:              in?   im   iw  29?o  2971   2m   im   im   2??s   mi

THYROID                              H                       N     N     N     H     N
  EPITHELIAL CYST                     -    (i)    <2>   £i)	(2)
  LWHOCYTIC INFILTRATE                          U)    -------
PAMTKfROID                          NNNNNHNNNN
TMCHEfl                              NNNNNNNN
  LTHPHOCYTJC  INFILTRATE               	
                                          NNNNNHNNH
       sum                               N           N           KM           N     N
  ECTASIA, MEDULLA                    1      -     i      -     t     -     -     2
LUN6                                                                                       N
  LWHOCYTIC INFILTRATE,PERM         <2>    <2>    <2)        <2>    (I)    <3>    <2)
  1NFW1, 1NTERST1TWL CHRONIC         <1)    <1)    <2)     -     -     <1)    (!)    <2>
  HICTJOCYTDSIS                       	----
HB«T                                                        N           N     N
  INFLATION, CHRONIC               <1>    (I)    (2)    <2>          <1>          -     <2>    (1)


AORTft                                HNNNNHNHNN


COLON                                N      N     N     N     N     N     N     N   "  N  •   N
                               CRepuft  Continued)
                                                111-44

-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                              ORTHO-CRESOL
                                          STUDY NO. 5221,OS
                               .  •         SPRAGUE-DflMlEY RATS
                               Tabulated  Animal   Data
                   WOJECT ID;  OCRESOL     GROUP:  173ia/KB    SEX: WLE      MYS;  AIL
                   PrtSE 8                 FATES; All
         flNIMAL ID. NO;               mi   2948   296?   2970   2971   2??2   2P73   2??4   2?75   2976

                                      NHNNNHNNNN

FSI8ESTOWCH                            NHNNNHNNNH

                                      HHNNNKNNNN

SKIN                                  NHNNHHNNHH
SKELETAL MUSCLE                        NNNNNHNNNK
LIViR                                       N      N     N      H     H      N                  N
  INFWfWTION, CHRONIC                <1>	<1>    .-
  WLCULUS                             -     -      -     -      2     -      i     -      -     -
                                Cisport Continujd)
                                                  111-45

-------
                          PATHOLOGY  ASSOCIATES,   INC

                                              ORTHfl-CiESOL
                                           STUDY NO. 52?!. U
                                          SPRAGUE-MULEY MT3
                                Tabulated  Animal   Data
                   PROJECT IDs OCRESOl     6ROUP;  175N6/KG    SEX: IW.E       DAYS; ALL
                   PftGE 9                 FATiS:  ALL
                IB.  HO:               2967   2?AS   2969   2970   297!   2972  2973   2?74   2975   297i

TESTES                                NNNNNNNNNN
PROSTATE                               N      N     N      N            N     N                   N
  LYMPHOCYTIC INFILTRATE                                         <2>     -     -     <1>    
EYES                                  NNNNN            NNNN
  mimi ATROPHY                      -            -      -     -      2
                                 (Report Continued)
                                                   111-46

-------
                                    PATHOLOGY  ASSOCIATES,   INC

                                                        ORTHO-CRESCL
                                                     STUDY NO,  5221.04
                                                    SPRAGUE-WJLEY iMTS
                                          Tabulated  Animal   Data
                             PROJECT ID:  QCRESDL     SROUPi  1?»G/KS    SEX: MALE       DAYS; ALL
                             WOE 10                FATES;  AU
                          ID, NO:               2947   2941   2949   2970   2971   2972   2?73   2974   2??5   297^

OTHER  TISSUES AND LESIIHS:

         HESENTERY-FAT NECROSIS                  -      .....     (2)
                                               oi Riport)
                                                             111-47

-------
                          PATHOLOGY  ASSOCIATES,   INC.

                                             QSTHO-CRiSOL
                                          STUDY HO,  5221.04
                                          SPRASUE-P4CT RATS
                                Tabulated  Animal   Data
                   PROJECT ID; OCRESQL     GROUP', 175HG/KG    SEX:  FEWLE     MYS; All
                   W6E  1                 FATES; ALL
                ID. MO;               3(JB9  30?0   3091   3052   30?3   3094  3093   SD9*   3fl?7   3091

BftUN           •                      HNNNNNNNNN


SCIATIC NERUE                          NNNHNNHNNN


SPIJWL CORD                            NNNNNNNMNN


eQNE                                  NNNNHNNNNN


BCf.I mRROU                            NHNNNNNNNN


SALIVARY SUHD                         N     H     N      M     H      N     N     H.N     N
WNDIBULAR LYMPH NODE                         N                  N                  H
  LYMPH01D HYPERPLAS1A                  3-22-1      t     -      2     1
THYHUS                                                                N           H      N
  HEMORRHAGE, ACUTE                   <2>        {]>    <»   (1)     -    (!)    -      -    (1)
PflNCREAS                               NHNNN         .  N.     N      N     N
  LWHOCYT1C INFILTiflTE                -     -      -      -     -     CD     -
P1TU1TAIY                              NNNNNNNMHN
                                (Report Continued)
                                                  III-48

-------
                          PATHOLOGY  ASSOCIATES,  INC.

                                             GR7HO-CFESOL
                                          STUDY NO, 5221.Oi
                                         SPRAGUE-WULEr RftTS
                               Tabulated Animal  Data
                   PROJECT 1C:  UCRESCL     BROUP: 175MG/K6    SEX; F&WLE    MYS; All
                   MBE 2                 FATES; ALL
                J&. NO:               308?   3090   30*1   30?2   3093   3094   3095   3094   3597   30?8

THfROlQ                               N           N      N     N                  N            N
  EPIMLML CYST                      -    -     <2>
WM1HYROID                            ONNHNNNUUN
1RACHK                                     NNHNNNNNN
  LWKQCYT1C INFiLTWTE               <1>	
BOPWSUS                              NNNNNNNNNM
ADRBWL iLWD                          N            N                         N     N     N      N
  ICTAS1A, HEDULW                     -      1     -      1      I      1      -     -     -      -


LUNS
  LWHOCYTIC )NFlLTWTE,PIRiy          <2>    <]>    <3>    <2)    (5)    <2>    <1>    (2>    <2)    <2>
  1HFW1, INTERfTITWl CHRONIC           -      -     <2>     -      -     <1>     -     -     <1>
  Hisriocrrosis                                         	
HEART                                 N      N     N            N            H     N            N
  INFltftWlCN, CHRONIC                 -      --(!)-
-------
        PATHOLOGY  ASSOCIATES,   INC.

                           GRTHQ-CRESOL
                        mm NO,  5221.04
                       SPSAGUE-OftULEY 1WTS
             Tabulated  Animal   Data
PROJECT  10: OCRcSOL    ORQUP: 175HQ/KS    SEX; FBtfLE     MYS; ALL
PAGE  3                 FATES: flU.
DUODENUM
                ID. NO:
                   30B9   3fl?0   3891   30?2   3Q?3   309^   30?5   30?4   30f7   3fl?8

                   HNHNNNNHNN
                   NNNNHNNNNN
GUWDUWR  JTOHflCH
                   HNNNNNNNNH
SKIN
                   KNNNNNMNNN
                   NNNNNNKNNH
SKELETAL
                   HNNNNNNHHH
LIVE!
                   NNNNNNNNHH
SPLEEN
  HBIOSIDEiOSIS
                   N      N     H      N     N
                                                    2212
KIDNEY
  NEPHRflMTHY, CHRCNIC
  LWHOCYTIC INFKWTE
  HYORONEPHROSIS
                   N      N            N      N      N            N            N
                   -      -      1      ------      2
                   ......     
-------
                          PATHOLOGY  ASSOCIATES,   INC,

                                             ORTHOCRESOl
                                           STUDY NO. 5221.04
                                          SP8AGUE-MULEY RATS
                               Tabulated  Animal   Data
                   PROJECT JO:  OCRESOL     CROUP; 175MG/KG    SEX;  FTOIE     MYSi flU
                   PASE 4                 FATES; ALL
                ID, NO;               3089   30fS   30JS   W2   33J3   3094   3SJ5   3fl?6  309?   3fl?8

QWRY                                 NNNNNNHNNH


UTERUS                                 NNNNN-NHNNN


EYES                                  HNNNNNNNNN


CERVIX                                 NNNNNNNNHN
                                (Report  Caatinued)
                                                  111-51

-------
                                    PATHOLOGY  ASSOCIATES,   INC

                                                       OffTHfl-CRESDL
                                                    STUDY NO,  5221,04
                                                    SPfWGUE-WLEY SATS
                                         Tabulated  Animal   Data
                            PROJECT ID: UCRESCl     GROUP; I731G/KG    SEX; FEMALE     DAYS: ALL
                            PAGE 5                 FATES; ALL
                       i ID. NO:                3089   30fO   3fl?i   3392   38?3   30?4   30?5   3fl?6   30??  3098

OTHER TISSUES AND LEillNS:
                                          (Rspcrt  Continued)
                                                            111-52  '

-------
                          PATHOLOGY  ASSOCIATES,   INC,

                                              Qra-CRESOL
                                           STUDY NO, 522S.04
                                          SPMUE-MULEY RATS
                                Tabulated  Animal   Data
                   PROJECT 10: OCRESOL     GROUP; I75MG/K6    SEX; FEWLE     CttYS: ALL
                   W6E  i                 FfflES; flU.
         WIMflL ID, NO:    •'          3099   3100   3101   3102   3103   3184   3103   3106   3107   31D8

«M1H                                 NNNNNNNNNN


SCIATIC NEWE                          NNNNNNNNNN


SPIfttL CURD                            NNNNNNNNHN


BINE         •                         NNNNNNNNNH


mi HARROU                            NNNNNNNNNxN


        fiWND                         NNN.NMNNMNN
          LWHNODi                                      N                               N
  LWHOIO HfPERPlASW                  312-2222-1
TKtWUS
  HEHORRW6E, ACUTE                   (2)    <1>    <2)    <2)    <1>    
  • <2) CYST ---- JWCREAS N N N N N N N LYMPHOCYTIC INFILTRATE CD ttlWR ATROPHf (1) --- PITUITARY NNN NNNN'NN CfST ---
    -------
                             PATHOLOGY  ASSOCIATES,   INC
    
                                               DRTHfl-CRESOL   •
                                             STUDY NO. 5221.04
                                            SPRAGUE-OAULEY RATS
                                  Tabulated Animal   Data
                      PROJECT ID; OCRESOL     GROUP: 1731S/XS    SEXi FTOLE    DAYS: ALL
                      mi 7                FATES; ALL
             ANIMAL ID.  NO:              30??  3100   3101   31(12   3103   3204   3105   3104  310?  3108
    
    THYROID                                    M                ,                    H     N
      EPITHELIAL CYST                    <2>    -     <2>    <25        (2)         -     -    <1)
      LWPHOCYTIC INFILTRATE                                       <2>	
    WlMTKYROIB                          NN^NNNNNNUH
    TWCHEA                              NNNNNNN           NN
      LYMPHOCYT1C  INFILTRATE               -------    <2)
                                        NNHNNNNHNH
    «Ri«L 6LAND                         NHN           NNNN
            ,  MIDU11A                    ...]....
    IUN8
      LYMfHOCTTIC  INFILTRATE,PERW         <2>   <2>        <1>    <1)   <1)   
      INFLAH, INTERSTITIAL CHION1C         <2>   <1>	CD
      H1ST1QCYTQSIS                       -     -     -      -     (1)     ----<»
                                        NNNNNNHNNN
    
    
                                        NNNNNHN.NNH
    
    
    COLON                                NNNNNNNN,NN
                                   (Report Ccntinuid)
                                                    ni-54
    

    -------
                               PATHOLOGY  ASSOCIATES,   INC.
    
                                                   ORTIIO-CRESOL
                                                STUDY NO, 5221.04
                                               SPWSUE-WAEY RATS
                                     Tabulated   Animal   Data
                        PROJECT ID:  SJCRESOL     SRBUPi  173HG/KG    SEX; FEWIE     MYS; AIL
                        PflCE 8                 FflTES;  ALL
    DUQDENUN
                     ID. NC:
                                          30??   31GO    3101   3102   3403    311H   3105   3!0d   3107   3108
    
                                           NNNNNNNNHN
    FORESTCHACH
      CCNSESTION
                                           NHNNN            NNNK
                                           .....      1
      wsi'wo STUWCH
                                           NNNNNNHNNN
    SKIN
                                           NHNNNNHNNH
    FWtttRY GLA.D
                                           NNNNNNNNNK
    SKELETftL MUSCLE
                                           NNHNNNHNNN
    LIUER
      1NFL^*«TION1 CHION1C
      LWPHOCfTIC  INFILTRATE
                                           N     N             N     N      N      N     N
                                           -     -          -
    SPLEEN.
      HEH051DEROS1S
    KIDNEY
      NEPHRQPATHY,  CHRONIC
      MINERALIZATION
      LYMPHOCYTIC ]NFlLlRftTE
                                           N     N
                                                                     
                                                                                  
    -------
                              PATHOLOGY  ASSOCIATES,   INC.
    
                                                 OCTHO-CRESOl
                                              STUDY NO. 5221.06
                                             SPIWSUE-MULEY BATS
                                   Tabulated  Animal   Data
                      PROJECT ID: OCRESOL     fiRQU?: 175MG/KG   SEXi FTOLE     DAYS: ALL
                      MGE 9                FATES: ALL              "              •   '.
                    ID. NO;               30??   3100   3101    3102   M03   3!Q4   3iQ5   3S04   310?   3J08
    
    mimm BLADDER                       NNNNNNNHN
      WFWrtttTIDN, ACUTE                  	                        
    -------
                                        PATHOLOGY  ASSOCIATES,   INC.
    
                                                            ORTKO-CRESQL
                                                         STtiW NO, 5221.OS
                                                        SP5WGUE-DAULEY RATS
                                             Tabulated  Animal   Data
                                 PROJECT IB:  QGRESBL     IROUP;  1731G/X6    SEX;  FEWLE     DAYS: ALL
                                 WEE 10                FATES; All
                       ffUMAL  JD. NO:               30??   310(1   31D1   3102  3103   3104   3105   3104   3107   3108
    
    OTHER TISSUES (W LESItNS;
                                               (End of Report)
                                                                 111-57
    

    -------
                               PATHOLOGY  ASSOCIATES,   INC.
    
                                                  OSTM-CR1SQL
                                                STUDY NO, 5221,06
                                               SPMGUE-MULEY  SATS
                                    Tabulated  Animal   Data
                       PROJECT  ID; OMESOL     GSOUPi ^OHE/KG    SEX: MALE      DAYS: ALL
                       WGE I                  FATES: ALL
              flNIHAL ID. NO;                29S4   2990   2991   2992   2973   2994   2995   2994   299?  2991
    
    ifWIN                                  NNNNNNNNNN
    
    
    SCIATIC NERVE                           NNNNNNNNNN
    
    
    SPtfttL CORD                             NNNNNNNNNN
    
    
    WNE                                   HNNNNNHHNN
    
    
    BONE HARROU                             NHNNNNNNNN
    
    
             GLAND                          HNNNUNNNNH
              LYHPH NUDE                         N                   U                         N      N
      CON5EJT10N                           3      ---------
      LYMPHQII HYPESPLAS1A                               J      2      -      2      !      1
    THWUS                                N                         A
      HMOWWGE, ACUTE                    -     <1)     <2)            
    -------
                              PATHOLOGY  ASSOCIATES,   INC.
    
                                                 ORTHO-CRESOl
                                              STUDY HO.  5221.04
                                              SPRAGUE-MUIEY RATS
                                   Tabulated  Animal   Data
                       PROJECT ID: OCRESQL     SROUP: ^BOMB/KG    SEX:  mil       MYS: ALL
                       PAGE 2                 FATES: ALL
             (WHAL ID. NO:
    
    THYROID
      EPITHELIAL CTST
      LYMPHOCYTIC INFILTRATE
                                         2W   299D   2991   2992   2993   2594  29?5   2994   2997   2993
                                                (2)
                                              '  (!)
                              (1)
                                                                          N     N
                                                                                      <2)
                                                                                                   <2>
    PARATHYROID
                                         NNNUNNNNNN
    TRACHEA
      LWPHOCYTIC INFILTRATE
                                         N      N     N            NNNNNN
                                                            <1)    ......
    ESOPHAGUS
      INFLAM1AT10N,  CHRONIC
                                          NH                  H      N     N      N     N     N
                                                      (])
    <3>
    
    <1)
    
    <»
                                                             22
                                                            (2)    (31
                                                             -    <2)
                                                            <2>
                                                                         (2)     <2)    <2>
                                                                          -3-
                                                                          -     131
    
                                                                         <2>     
    ffiART
      INFLAltWTIDN,  CHRONIC
                                         N      N            N     N      N     N            H
                                         -                     (1)
                                    (Report Continued)
                                                      111-59
    

    -------
                             PATHOLOGY  ASSOCIATES,   INC.
    
                                                QRTHO-CRESOL
                                             STUDY NO, 5221.OS
                                            SPRAGUE-OAULEf RATS
                                  Tabulated  Animal  Data
                      PROJECT 10: OCRESOL     GROUP; 400MS/K8    SEX: miE      DAYS: ALL
                      PAGE 3                FATES: AH
             ANIMAL ID. NO:               2984   2990   mi   im   2m  2m  im   wt>   2m   im
    
    AORTA                                NNNNNNNNNN
    
    
    COLON                                NNNNNNNNNN
    
    
    TOENlfl                             NNNN.NNNNNN
    
    
    FORESTOrMCH                          NNNNNNNNNM
    
    
    6UMDUUK STDfttCH                     NNNNNNNNNN
    
    
    SKIN                                 NNNNNNNNNN
    
    
    rm*WY SL^D                         NNNUNNNNUN
    
    
    SKELETAL MUSCLE                       NNNNNNN-NNN
    IMR                                      N     N            N     N     N     N     N
      CTOE5TICN                        121    -     -     <2>	
      NECROSIS,  CUMULATIVE               ---	
      lYMPHOCYTIC INFILTRftlE	
    -------
                               PATHOLOGY  ASSOCIATES,   INC.
    
                                                   ORTHD-CRESOL
                                                STUDY NO. 5221.04
                                               SPWGUE-OAULEY EATS
                                    Tabulated  Animal   Data
                       PROJECT ID:  OCSESOl     GROUP; dOONG/KG    SEX: WLE       MYS; AU
                       Ml 4                 FATES: ALL
              WML ID. NO:                2984    2??D   29?1    2??2   2993   2?94   29?5   Wt,   2?97   2998
    
    KIDNEY                                 N     N      N      N      N            N      K
      NEPHROPATHY, CHRONIC                                                   I      -      -      1      1
    URINARY BUDOER                         N     N            N      N      N     N      N
      LWPHOCYTIC  INFILTRATE                -     -     (35	
      CALCULUS                                           2	1
    TESTES                                       NNNNNNNNN
      ATROPHY, SEMINIFEROUS TU8ULE          (1)     	     ....
    PROSTATE                                NN            NNNNNNN
      LYHPHOCYTIC IffflLTWTE                 -      -     <3>	
                                           NNNNNNNNNN
                                     (Report Continued)
                                                       111-61
    

    -------
                                      PATHOLOGY  ASSOCIATES,   INC.
    
                                                         QRTHD-CRESQL
                                                      STUDY NO. 5221.04
                                                     SPRAGUE-MULEY RATS
                                           Tabulated  Animal   Data
                               PROJECT ID;  OCRESOL    GROUP;  iflflhG/KG   SEX; mil      DAYS: ALL
                               PAW 5                ftfllS:  ALL
                            18. HO;               2J84   2»0   2W   W?2   2J?3   2?f4   2??5  19U
    
    OTHER TISSUES AND LESIWSi
                                            (Report Centinued)
                                                              111-62
    

    -------
                              PATHOLOGY  ASSOCIATES,   INC.
    
                                                  QRTKO-CRiSOL
                                               STUDY NO. 5221.fli
                                              SPRA6UI-WULEY IWS
                                   Tabulated  Animal   Data
                       PROJECT ID: OCSESOL     SROOP: ^OflMS/KS    SEX; MLE  •   > OftYS; Ail.
                       PAGE j                 MTEi: ALL                    '•  •'
             (WimL ID.  NO:               2999  3008   3001   3082   3Q03   3004   3035   300(S   3007   3008
    
                                          NKNNHHNNNN
    
    
    SCIATIC NEWE                          NNNNNNNNNN
    
    
    SPIWL CCRO                            NMNNNNNNNN
    
    
    8(WE                                  HNNNNNNNNN
    
    
    BONI WRROU  '                          NNNNHNNNNN
    
    
    SALIVARY BUW                         NNNNNNNNNN
    IWD1IUWR LWPH NODI                         N      N           N                         N     H
      CtKSESTION                           	2-3--
      LYMPHOID (ffPERPLASIA                  1      -      -     I     -      -     2
    TOUUS
                                         <2>     <2>    U>    <1>    <2>    <2>    <1)    (3)
    IWCSKS                               NNNHNNNfl           N
      LWPHOCYTIC INFJLTWTi                	'-
    -------
                               PATHOLOGY  ASSOCIATES,   INC
    
                                                  ORTHO-CRESOL
                                               STUDY NO.  5221.Qd
                                               SPRAGUE-BAULEY RATS
                                    Tabulated  Animal   Data
                       PROJECT  ID: OCRESOL    GROUP; iOOMG/KG    SEXi fWLE       MYSi  ALL
                       PAGE 7                 FATES: All
             MWL ID. NO:                2???   3(100   3001   3002   3003   3004   3005   3004   3007   3008
    
    THYROID                               N      N                   N     N            AN
      EPITHELIAL CYST                      -      -      -     (2)     -     -     <1)     -      -    (U
      IWHOCmC INFILTRATE                             <2>	
      INFUWfflGN, GRANULGWTOUS           -      -      3      .-.---.
    WRATHYR010                            HNNNNNNNNN
    TRACHW                               NNNNN             NANN
      CONiESTION                           	2
      INFLATION, ACUTE                  	----
    iSQPHASUS                              NHKNHNMNNN
    ADREWL GLAND                          NNN            NNNNNN
      ECTASIA, MEDULLA                     ...      j     ......
    LUNfi
      LWPHOCTTIC INFILTWTE.PERW          <2)    <2)    <25    <25    <1)     -     <1>    <3)    <1>
      1HFLAM,  IffTEISTITIAL  CHRONIC          <]>-<»-
      OIL ORDPLETS                         -      2      -      -      -      2      -     3      -     I
      C(W6EST1(W                                 C31           -      -     [31     -    [31     -    <2>
      EDEMA                                     <2>           -      -     <2)     -    <2>     -    <2>
      HEMORRWGE                           -{[)-           <2)
                                     (Rjport Continutd)
                                                       in-64
    

    -------
            PATHOLOGY  ASSOCIATES,   INC.
    
                               GR7HO-CRESOL
                             STUDY NO, 3221.04
                            SPRAGUE-MULEY SATS
                 Tabulated  Animal   Data
    PROJECT  ID: OCRESOL     GROUP: 400HG/KG    SEX: WLE       DAYS: All
    PAGE 8                  FflTES: ALL
    AORTA
                     ID. NO:
                       25*79   30DQ   3001   3002   3083   3004   38B5   300^   300?  3008
    
                        NHNNNNNNNN
    COLON
                        NNNNNNNANN
    DUODENIW
    
    
    FORESTWCH
                        NNNNNANflNN
                        NNNNNNHNNN
              STOWCH
      D1WT1DN,  6LAND
                                            NNNHNNH
    SKIN
                        NNNKNNNNNH
            SWND
                        NNNNNNHNNN
    SKELETAL HUSCLE
                        NNNNNNNNNN
    LIVER
      CONSESTIflN
                        N            NNNNNNNN
                        -2      ........
    SPLEEN
      HEHOSIOERDS1S
                        1       1      1      2      1
                                                         N     N      N      N     H
                  (Report  Continued)
                                     111-65
    

    -------
           PATHOLOGY  ASSOCIATES,   INC.
    
                              ORTHO-CRESQL
                           STUDY NO,  5221.04
                           SPWtGUE-MULEY FMT5
                Tabulated  Animal   Data
    PROJECT ID!  OCRESDL     BRQUP; 6DOHG/KB    SIX:  mil       WYSi All
        ?                 FATES: All
                    ID. NO;
    KIDNEY
      NEPHROMTHY, CHRONIC
                      2W  3030   3B01   3002   3003   30 M   3005   3D04   3007   3008
    
                       N                               N     N     N      N     N
                             i      1      1      I      .....
    URINARY IL/WDER
                       NNHMNNH            NN
                       .......     2
    TESTES
    
    
    PROSTATE
                       NNMHNNNHNN
                      CD
                                                      N      N
                                                                          N     N
    EYES
      CATAWCT,
                       NNNNNNNNN
                 (Report Continuid)
                                   111-66
    

    -------
                                      PATHOLOGY  ASSOCIATES,   INC
    
                                                         ORTHO-CRKOL
                                                      STUDY NO. 5221.0(5
                                                     SPRAGUE-MULEY HATS
                                           Tabulated  Animal   Data
                               PROJECT 10;  OCHESOl    iROU?;  400MS/K3   SEX; «&E      DAYS: ALL
                               W6E 10               FATES:  flLL
                      (Him. ID,  NO:               29?9   3000   3001   3002   3803   30D4   3005   3304  3007   3008
    
    OTHER TISSUES (WO LESIONS:
                                            (Report Cofttinytd)
                                                            111-67
    

    -------
                              PATHOLOGY  ASSOCIATES,   INC,
    
                                                 08THQ-CRES3L
                                              STUDY NO. 5221. IM
                                              SPRft6UE-WWLFf RATS
                                   Tabulated  Animal  Data
                       PROJECT ID; QCRESOL    6SOUP; AOOHS/KS    SH: hftLE      DAYS: ALL
                       PAGE 11               RTES; ALL
             (WIHAL ID, NO:               300?
    mm                                 N
    
    SCIATIC NERUE                          N
    
          CORD                            N
    IONE
    
    
    ONE WtRRCU
    
    
    SALIVARY
    IWOliUWR LYMPH NODE
      LWKDID HYPERPWSW
    THYKUS
              E, ACUTE                    
    -------
                              PATHOLOGY  ASSOCIATES,   INC
    
                                                 ORTHO-CRESQL
                                              STUDY NO. 5221.06
                                             SPRASUE-WWLEY RATS
                                   Tabulated  Animal  Data
                      PROJECT 10; OCRESQL     SROUP;  400MG/KG    SEXi WLE      DAYS; ALL
                      flftCE 12               FATES:  ALL
                  i IB. HO;              300?
    
    PA1MTHYROID                           N
    
    
                                    •     N
    ESOPMGUS
    ADRENAL  5UWD
      ICTASIA, MEDULLA
    L1M
      LYMPHDCYTIC INF1LTMTE,PER!M          
    HWRT
    
    
    AORTA
    
    
    COLON
    
    
    DUODE34LH
    
    
    FOREST'DWCH
    
    
    BU5HDULAR
                                    (Report Continued)
                                                     111-69
    

    -------
                               PATHOLOGY  ASSOCIATES,   INC.
    
                                                  CRTHO-CRESOL
                                               STUDY NO.  5221.04
                                              SPRAGUE-DAULEY »TS
                                    Tabulated  Animal   Data
                       PROJECT 10! OCRESDl     SROUP;  MOMS/KG    SEX; MALE       DAYS: ALL
                       PASS  13                FATEii  fill
                    10.  HO:               300?
    
    SKIN                                  N
                                          U
    
    
            MUiCL!                        K
    LIVER
      INFWWTJON, CHRCN1C
    
    
    SPLEEN
    
    
    KIDNEY
      mmmm, CHRCNIC
    
    
    URIfWRY  BWDOER
    
    
    TESTES
    
    
    PROSTATE
    
    
    EYES
                                            CiJtitinusd)
                                                       111-70
    

    -------
                                       PATHOLOGY  ASSOCIATES,   INC.
    
                                                          OHTHC-CRESOL
                                                       STUDY NO,  5221,U
                                                       SPRAGiJE-DAULO' »TS
                                            Tabulated  Animal   Data
                                PROJECT ID:  OCRESOL     CROP: WONG/KG    SEX:  MALE       DAYS; ALL
                                WOE 14             '   FATES: ALL
                             ID, NO:               3009
    
    OTHES TISSUES AND  LESIINS:
                                             (End of  Sepcrt)
                                                                111-71
    

    -------
                              PATHOLOGY  ASSOCIATES,  INC.
    
                                                 ORTHQ-CRESQl
                                              STUDY NO. 5221.06
                                             SPMGUE-fWJLEY IOTS
                                   Tabulated  Animal   Data
                       PROJECT  ID; QCRESOL     GROUP: MOMG/KB    SEX: FE»LE -   DAYS: ALL
                       W6E 1                 FATES; AH
                    ID. Nfl;              3112   3113   3121   3122  3123   3124   3125   3124  312?   3128
    
    BRAIN                                NNNNNNNNNN
    
    
    SCIATIC NERVE                         NNNNNNNNNN
    
    
    SPINAL CORD                           UNNNNNNNNN
    
    
    80NE                                 NNNNNNNNNN
    
    
    BCNE WRROy                           NNNNNNNNNN
    
    
            6UWD                        NNNHNNNNNN
    NWIBUWR LWH NOM                              N                         N
      HEHORRtWGE, ACUTE                    -     -     -     <2>.    -     -      -
      OW6EST1CN                          2     ...     2     -      -      2
      LWHOID HYPEHPWSIA                 I     2     -      2     2     J
    THfflUS                                      N     N                         N            N
      HEH08RIW6E,  flCUTE                   <1>    -     -     <1>    <1)    <2)     -     <2>     -
    MNCREAS                              NNNNNNNN-   NN
    
    
    PITUIWRY                             NNNNNNNNNN
                                    (Report Continuetl)
                                                     111-72
    

    -------
                               PATHOLOGY  ASSOCIATES,   INC.
    
                                                   CRTHO-CRISQl
                                                STUDY NO. 5221.06
                                               SP&GUE-DAULEY  RATS
                                     Tabulated  Animal   Data
                        PROJECT !D: OCRESOl     SROUP-. MCHE/KG    SEX: FEMALE     MYSi ALL
                        PAGE 2                 FATES; ALL
                     ID. NO:               3112   3113   3121   3122   3423   3124   3125   3!2A   3127   3128
    
    THYROID                                              N                    N      N      N     H      N
      EPITHELIAL CYST                     (1)    (1)      -    <2).        <2)
      OIL DROPLETS                         322-22-231-
                                           [33     -     -     [3J    li:      -      -     [31     13]    [33
                                           (2)     -     <2>    <2)    (1)     <3>    (2)    (2)     (!)
      HBiORRWGE                           -      -     -     <1>    <1)	
      lACIERIfl                             	<2)      -      -
    HEART                                  NNNNNNHNNN
    
    
    AORTA                                  NNNNNNNN'HN
                                      (Riport
                                                         111-73
    

    -------
            PATHOLOGY  ASSOCIATES,  INC.
    
                               OETHO-CRESOL
                            STUDY NO. 5221.04
                           SPRAGUMMULEY MTS
                 Tabulated  Animal  Data
    PROJECT ID: OCRESOL     GROUP:  600HS/K5    SEX: FBW.E     DAYS; ALL
    PftGE  3                 FATES:  ALL
              ANIMAL ID. NO:
    COLON
                      3J22   3113   3123   3S22   3123   3124   3125   3124   312?   3128
    
                       NNNNNNNNNN
    WJODEMJH
                                          NN
                                           NNNNNNN
    FORESTGfttCH
                       NNNNNNNNNN
    JWIOUWR  STOW*
                       NNNNNNNNNN
    SK]N
    
    
    JWtWIW  SLM)
    
    
    SKELETAL MUSCLE
                       N      N      N      N      N      N      N     N      N     N
                       NNUNNNNNUN
                       NNNNNNNNNK
    LIVER
      CCNGEiTiaN
                       NNNNNNN            N
                       .......      2-2
    SPL1EN         •
      HMSIOEROSIS
                       NANNNN             NN
                       ......      2      -      -      2
    KIDNEY
      NIFHiflPATHf, CHRONIC
      INFLAmftTJDN, AWTE,  PELMIS
      CfST
                                          NNN
                                                                    NNN
                                                                           NN
                  (Rfport Continued)
                                    III-74
    

    -------
                             PATHOLOGY  ASSOCIATES,   INC.
    
                                                ORTKO-CRESOL
                                             STUDY NO, 5221,M
                                             SPMGUE-W4EY RATS
                                  Tabulated  Animal   Data
                      PROJECT ID: OCRESQL     iROUP;  WOHG/HS   SEX: FBttLE     MYS: ALL
                      MOE 4                 FATEi:  AU
             mmi ID. NO;               3112   3113  3121    3122   3123   3124   3125  3124   3127   3128
    
    mmm BLADDER                        NNHNNIINHNH
    
    
    WiRY                                 NNNNNNNHNH
    
    
    WESUS                                NNNNNNHNNN
    EYES                                 NHNNMNN           NH
      CATAIMCT, LENS                       	                  2
    CERVIX                               NNNNHNNNNN
                                   (Report  Continu»dJ
                                                   111-75
    

    -------
                                       PATHOLOGY ASSOCIATES,   INC.
    
                                                           1THO-CRESOL
                                                        STUDY NO, 5221,05
                                                                     MTS
                                             Tabulated  Animal   Data
                                PROJECT 15; CCRE30L     6ROUP: 4BCHS/K5    SEX; FEHM.E     DAYS; ALL
                                PAGE 5                 FATES; ALL
                      .(ttm. 10.  NO:
    
    OTHER TISSUES AND LESIINS:
    
             HESENTERY-FAT NECROSIS
             LAfflW-HEMORiWGE, ACUTE
             JEJtMH-NOBW.
             1LEUH-NORMAL
    3112  3113   312S   3122   JI23   3124   312S   3124   3127   3123
                                                       (3)
                                              (Report Continutd)
                                                               111-76
    

    -------
                               PATHOLOGY  ASSOCIATES,  INC.
    
                                                  ORTHQ-CRESOL
                                               STUDY NO. 5221.04
                                              SPRAGUE-DMLEY RA7S
                                    Tabulated  Animal   Data
                       PROJECT ID: QCfiESOL     GROUP;  iOW1S/K5    SEX: FEHALE     OftYS: ALL
                       PASE 4                 FATES:  All
                  i 10, NO:               3129   3130   3131   3132   3133   3134   3133   3$3    <1>    <2)    <2)        <1>
    
    
    WWCREAS      .                         NNANNAN            NN
      LYMPHOCYTIC INF1L1MTE                	(13     -     -
    PITUITARY                              N     N      N     N      N      N      N     N,N     N
                                     (Repsri Continued!
                                                       111-77
    

    -------
                              PATHOLOGY  ASSOCIATES,   INC.
    
                                                  ORTHQ-CRISQL
                                              STUDY NO, 3221.06
                                              SPWGd-MUlEY RATS
                                    Tabulated  Animal   Data
                       ROJECT ID;  OCRESOl     SRCUP: iOOMG/KS    SEX: FTOLE     DAYS; AIL
                       WGE7                 FATES! All
             ANIWL 10. NO:               312?  3130   3131   3132   3-133   3134   3S35   3136   3137   3138
    
    THYIOID                                N            A     N            N                  N
      EPITHELIAL CYST                      -        <2>     -     (2)
      LYMPHQCYTIC INFILTRATE                	U>
    PARATHYROID                            NUUNUNNNNH
    TRACHW                                NNNNNNKNNN
    ESOPHAGUS                              NNNNNNNNN
                 , CHRCN1C                 .........     (2)
           6LWD                          N           NNNNNNNH
      ECTftSW, HIOULLA                           1     -..--..-
    LUNS
      L1WHOCYTIC 1NF3LTRATE,PE11V         
      IWfH, 1MTERSTITWL CHSDNIC                            <2>     -     <2)
      OIL  DROPLETS            '             -     -      3     (1)     -      3     -      -     2      2
      C»GESTIQN                          C31     -     <3>    C31    <2>    <2>    -      -    <3)    CIS
      mm                               <2>     -     w    <3>     -     <3)    -      -    <2>    <3>
      HMRRHflEE                          (1!     -      -     (1)     -     (1)    -      -     -      -
      H1ST10CYTOSIS                        -     -           (2)           -     -  '    -
      FNEUHCNW, FDREI6N BUOY               	---
      PNEIMCNW, CHRONIC-rtCTlUE             -     -      -     <3)	
                                                NNNNNNN,  NN
                 ,  CHRONIC                <2>	-
                                    (Report Continuid)
                                                      111-78
    

    -------
            PATHOLOGY  ASSOCIATES,   INC
    
                                QKTHfKRESDL
                             STUDY NO,  5221,04
                            SPIWGUE-DAULEY RATS
                 Tabulated  Animal   Data
    PROJECT ID: OCRESOL     GROUP!  iOOMG/KG    SEX: FBttLE     DAYS: ALL
    mi 8                 MIES:  ALL
    AORTA
                     ID. NO:
                       3129   3130   3131   3132   J133   3131   3135   3134   3137   313S
    
                        N      N'N      N      N     N      N      N     N      H
    COLIN
                                           NN
                                                               NN
                                                                NNNN
    DUODENUM
                        NNANNANNAN
    FCRESTWCH
                        NNNNNNNNNN
              STWCH
                        NNNNNNNNNH
    SKIN
                        NNNNNNNNNN
           8WNO
    
    
    SCILETALMUSCLI
                                           NNNNN
                                                                NNNN
                        NMNNNNNNHN
    L1VEI
      OT6ESTIDN
      LYHPHOCrriC  INFILTRflTE
                       <1)
                              N             NNNNNHH
                                     1      .......
    SPLEEN
      HEHDSIDEROSIS
                                     N      N      N     N                   N      N
                        2      2      -      -      -     -      i      2
                  
    -------
                              PATHOLOGY  ASSOCIATES,   INC
                                               STUDY NO. 5221.04
                                              SPRAGUE-MULDf  RATS
                                    Tabulated  Animal   Data
                       PROJECT ID: OCRESOL     8ROUP; fl>OM8/K6    SEX;  FEMALE     DAYS: ALL
                       PAGE 9                 FATES j AU
    L ID. NO:
    KIDNEY
      NiPHRQPATHY, CHRONIC
      HTDRCNEPHiOSIS
                                         3129  3130   3131   3132   1133   3134   3135   3!34   3137   313B
                                               1      1
                                                            N     N      N     A     H
    URIfWTf BWOOIR
                            NNNNNNNNMN
    DWRY
                            NNNNNNNNMN
    UTERUS
                            NNHNNNNNNN
    EYES
                            NNHNNNNNNN
    CERVIX
                            NNNNNNNNNN
                                    (Report  Continued)
                                                      111-80
    

    -------
                                        PATHOLOGY  ASSOCIATES,   INC
    
                                                           ORTHO-CESOl
                                                        STU9YNC. 5221,06
                                                       SPfWSUE-OAULEY RATS
                                             Tabulated  Animal  Data
                                PROJECT IDi CCRE50L     GROUP:  40W6/KO    SEX: FEMLE     DSYS: SLL
                                ME  10                FftTES: ALL
                             ID. NO:               31251   3130   3131   3132   3133   3134   3135   3134   3137   3138
    
    OTHER TISSUES AND LES1WS:
                                                               111-81
    

    -------
                              PATHOLOGY  ASSOCIATES,   INC
    
                                                ORTHO-CRESQl
                                             STUOY NO. 5221.U
                                             SPRAGUE-MULEY RATS
                                   Tabulated Animal   Data
                         JEn ID: QCRESOL     BRQUP: dflONS/K6    SEX; FEmiE     DAYS: ALL
                      M3E 11                FATES; ALL
             ftNIHAL  ID. NO;               313?  3140   314!
    
    BRAIN                                N     N     y
    
    
    SCIATIC NEWE                         N     N     H
    
    
    SPIWL CORD           '                N     N     N
    
    
    BONE                                 N     N     N
    
    
    BONE WRROU                           N     N     N
    
    
    SAL I WRY GLAND                        N     N     N
    (WTOJBUWR LYMPH NODE                        H     A
      LfHPHOJD HYPERPLASIfl                 3
    1WMUS                                            ft
      HEWORRM6E, ACUTE                   
    -------
                              PATHOLOGY  ASSOCIATES,   INC.
    
                                                 OR1HO-CRESOL
                                              STUDY NO. 5221,OJ
                                             SPRASUE-MULEY SATS
                                   Tabulated  Animal   Data
                       PROJECT ID; DCRESOL    SROUP:'400HG/KS   SEX: Fimi£     DAYS: ALL
                                            FATES: ALL
             ANIttfl ID, NO:               3139   3140   3141
    
    TKYROiD                                      N
      EPITHELIAL CYST                     <2>     -    (13
      LYMPHOCYTE llfflLTMTE               (1)
                                         K     N      H
    
    
    TRACHEA                               N     N      N
    
    
    ESOPWGUS                             H     N      H
    
    
           BLANO                         H     H      A
    L1M
      LYMPHKYTIC INFILTRATE,PIR1V          <1>    «)    <2)
      1NFLAM, 1NHRST1TIAL CHRONIC          <1>    <2>    <2>
      OIL DMPLETS                        -      1      2
      CDNBESTltW                          -     (3)
      EDBtt                               -     <2)    <2>
      HlfTIQCHOSIS                       -     (1)     -
      WEIWDNW, CHRONIC-ACTM            -      -     <2>
    HiW                                 N     N      N
    
    
    AORTA                                 N     N      H
    
    
    COLON                                 N     N      H
                                    {Report Continued)
                                                      111-83
    

    -------
                              PATHOLOGY  ASSOCIATES,   INC,
    
                                                 ORTHO-CRISQL
                                              STUDY NO, 5221.06
                                             SPRftGUE-MULEY MTS
                                   Tabulated  Animal   Data.
                       PROJECT ID: OCRESGL     BROUP; iOCHQ/KS   SEX: FEWLE     DAYS! ALL
                       PAGE 13               FATES: ALL
    KJOOENIH
                    ID, NO:
                                         3139   3140   31 «
    
                                         N      N      N
    FQRESTOWCH
                                         N      N      N
    SUW1JWR .STITCH
                                         N      N      N
    SKIN
                                         N      N      N
           8UWO
    
    
            MUSCLE
                                         N      N      N
                                         «     H      N
    LIVER
                                         N      N      N
    SPLEBi
      HHDSIDERSJSIS
    KIDNEY
      ffiPHROPATffif,  CHRONIC
      HYDRONEPHROSIS
           BWDDER
                                         N      U      U
    mm
                                    (Report Confinutd)
                                                     111-84
    

    -------
                               PATHOLOGY  ASSOCIATES,   INC.
    
                                                  ORTHB-CRESOL
                                               STUDY NO, 5221.06
                                              SPRAGUE-WJLFf RATS
                                    Tabulated  Animal   Data
                       PROJECT  10: OCRESOL     6ROUP:  ^OOHG/KG    SEX:  FEmiE     MYS; AIL
                       PfiGE  14                FATES;  fill
                    ID. NO;               3139   3140   3141
    
    UTERUS                                N      N     K
    
    
    EYES                                  N      N     N
    
    
    CERVIX                                N      N     N
                                            ContinytdJ
                                                       111-85
    

    -------
                                     PATHOLOGY ASSOCIATES,   INC.
    
                                                       OiTHO-CRESOL
                                                     STUPY NO, 5221. Oi
                                                                 RATS
                                          Tabulated Animal   Data
                              PROJECT ID;  QCRESOL     GROUP; 4flDHi/K6   SEX; WHLE    MYS; AH
                              MGE 15               FATES; ALL
                            ID. NO:              313?  3NO   3HI
    
    OTHER TISSUES AND LESIINS:
                                           (End ri Report)
                                                            III-8S
    

    -------
    IV, GROSS VS. MICROSCOPIC FINDINGS
    

    -------
    

    -------
                           PATHOLOGY  ASSOCIATES,  INC
    
                                      ORTHO-CRESOL
                                   STUDY MO, 5221.06
                                  SPRAGUE-DAWLEY  RATS
                    Correlation  o-f  Gross  & Micro Finding-
    PROJECT ID: OCRE30L     GROUP; Q.OMG/KG    SEX: MALE       DAYS: ALL
    PAGE 1            ,      FATES: ALL
    
    
    ANIMAL NO; 2391            PATHOLOGY ID. NO: 852891            PATHOLOGIST; DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2892            PATHOLOGY ID, NO: 852892            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 91
    
    ..cFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NSL
    
    >                                        LARGE HAIR WITH ASSOCIATED
                                             INFLAMMATION IN MAJOR BRONCHIOLE
    ANIMAL NO: 2893            PATHOLOGY ID. NO: 852893            PATHOLOGIST; DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
                                  
    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221 ,Q6
                                   SPRAGUE-DAULEY RATS
                    Correlation  o-f  Gross & Micro  Findings
    PROJECT ID: OCRESOL "     GROUP:  O.QMG/KG    SEX:  MALE       DAYS:  ALL
    PAGE 2                   FATES;  ALL
    
    
    ANIMAL NO: 2394             PATHOLOGY  ID,  NO:  852S94            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                        '                DAYS ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTQPATHOLQSY;
    
    >SPLEEN-CYST ALONG MARGIN-CLEAR,       '  SPLEEN- CYST
     3X2MM
    
    >KIDNEY~SLIGHTLY MOTTLED AND  PITTED       NO COROLLARY CHANGE DETECTED
    ANIMAL NO; 2895             PATHOLOGY  ID.  NO5  852895            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
     ROBABLE CAUSE OF DEATH:                                        DAYS ON TEST; 92
    
    REFERENCE TO NECROPSY RECORD;            RELATED  HISTOPATHOLOGYi
    
    >NGL
    ANIMAL NO: 2896            PATHOLOGY  ID.  NO:  852896             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH-:                                        DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
                                   
    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO,  5221 .06
                                  SPRAGUE-DAULEY  RATS
                    Correlation o-f  Gross. &c Micro  Findings
    PROJECT ID: OCRESOL     CROUP: O.OMG/KG     SEX: MALE        DAYS: ALL
    PAGE 3                  FATES: ALL
    
    
    ANIMAL NO: 289?            PATHOLOGY  ID. NO:  852897             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH;                                        DAYS ON  TEST;  9\
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:                '
    
    >NGL
    ANIMAL NO: 2398            PATHOLOGY  ID. NO:  352898             PATHOLOGIST;  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    /NQL
    ANIMAL NO: 2899            PATHOLOGY  ID. NO: 852899             PATHOLOGIST;  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:  ,         RELATED HISTOPATHOLOGY5
    
    >MESENTERIC FAT-i OX3MM) ROUND DARK     MESENTERIC  LN-HEMORRHAGE
     NODULE.
    
    >LIYER-MOTTLED                           LIVER- NECROSIS,  GQAGULATIUE;  LIVER "
                                             LESION COMPATIBLE WITH FOCAL
                                             ISCHEMIA.   NO  ETIOLOGICAL  AGENT
                                             NOTED.
                                   (Report Continued)
                                        IV-3
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       QRTHO-CRESQL
                                    STUDY  NO.  5221. Q*
                                   SPRAGUE-DAUILEY RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL     GROUP:  Q.OMG/KG     SEX: MALE       DAYS; ALL
    PAGE  4                  FATES:  ALL
    
    ANIMAL NO:  2900            PATHOLOGY  ID, NO:  852900            PATHOLOGIST; DSC
    ANIMAL FATE;  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH;                                       DAYS ON TEST; 9i
    REFERENCE TO  NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    >INGUINAL LYMPH NODE-RIGHT               ING.  LN-LYMPHOID  HYPERPLASIA
     ENLARGEDCUITH MAMMARY  TISSUE)
    ANIMAL NO; 2901            PATHOLOGY  ID. NO; 852901            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TESTt 93
    
     EFERENCE TO NECROPSY RECORD;           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2902            PATHOLOGY ID. NO.- 852902            PATHOLOGIST; DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2903            PATHOLOGY  ID. NO: 852903           •'' PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATHs                                       DAYS ON TEST: 9c
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHQLOGY:
    
    >NGL
                                  (Report Continued)
                                       IV-4-
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAWLEY RATS
                    Correlation of  Gross & Micro  Findings
    PROJECT  ID:  OCRESOL  "    GROUP:  0.OHG/KG     SEX:  MALE       DAYS:  ALL
    PAGE  5                   FATES;  ALL
    
    
    ANIMAL NO: 2904             PATHOLOGY  ID.  NO:  852904            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH;                                        DAYS ON TEST: 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO:'2905            PATHOLOGY  ID.  NO:  852905            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  93
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
     ,-JGL
    ANIMAL NO: 2906            PATHOLOGY  ID. NO:  852906             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >MGL
    ANIMAL NO: 2907            PATHOLOGY  ID. NO:  852907             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH.-                                        DAYS ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
                                   (Report Continued)
                                        IV-5
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO,  5221 ,Q6
                                   SPRAGUE-DAULEY RATS
                    Correlation  o-f  Gross & Micro  Findings
    PROJECT  ID: OCRE30L  "    GROUP:  0.QMG/KG    SEX:  MALE       DAYS:  ALL
    PAGE 6                   FATES!  ALL
    
    
    ANIMAL NO: 2908             PATHOLOGY  ID.  NO:  852908            PATHOLOGIST;  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH 5                                        DAYS ON TEST; 93
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2?Q9            PATHOLOGY  ID.  NO:  852P09             PATHOLOGIST:  DSC
    ANIMAL FATE; SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH;                                        DAYS ON TEST:  93
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    ANIMAL NO: 2910            PATHOLOGY  ID.  NO:  852910             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD:            RELATED.HISTOPATHOLOGY:
    
    >NGL
                                   
    -------
                           PATHOLHGY ASSOCIATES,  INC
    
                                       QRTHO-CRESQL
                                    STUDY NO.  5221.04
                                   SPRAQUE-OAU1LEY  RATS-
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID:  OCRESOL      GROUP:  O.OMG/KG    SEX:  FEMALE     DAYS:  ALL
    PAGE  1                   FATES 5  ALL
    
    
    ANIMAL MO:  3023             PATHOLOGY ID.  NO:  353023            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOL08Y:
    
    >MGL
    ANIMAL NO: 3024             PATHOLOGY  ID.  NO:  853024            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  92
    
      iFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3025             PATHOLOGY ID. NO:  853025            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                            -            DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 302<5             PATHOLOGY  ID. NOs  853026            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:      •     RELATED  HISTOPATHOL06Y:
    
    >NGL
                                        IV-7
                                   (Report  Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221 .06
                                   SPRAGUE-QAWLEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL  .    GROUP:  Q.OMG/KG     SEX:  FEMALE      DAYS! ALL
    PAGE 2               "    FATES:  ALL
    
    
    ANIMAL NO; 3027            PATHOLOGY  ID, NO; 853027             PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF  DEATH:                       "                DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >HISTO-KIDNEY-i  C1X1MM)  CYST  IN         NO COROLLARY CHAN6E  DETECTED
     CORTEX OF RT. KIDNEY.
    ANIMAL NO: 3028            PATHOLOGY  ID. NO: 853028            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS  ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    ANIMAL NO: 3029            PATHOLOGY  ID. NOi 85302?             PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3030            PATHOLOGY  ID. NO: 853030             PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
                                   (Report Continued)
                                        IV-8
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221 .06
                                   SPRAGUE-DAWLEY  RATS
                    Correlation of  Gross &'Micro  Findings
    PROJECT  ID;  OCRESOL      GROUP;  O.OMG/KG     SEX:  FEMALE      DAYS:  ALL
    PAGE  3               -    FATES:  ALL
    
    
    ANIMAL NO; 3031             PATHOLOGY  ID. NO:  853031             PATHOLOGIST: DSC
    ANIMAL FATE;  SCHEDULED  SACRIFICE
    PROBABLE CAUSE  OF  DEATH:                       "                DAYS ON TEST:  92
    
    REFERENCE TO  NECROPSY RECORD;           RELATED  HI3TOPATHOLOGY:
    
    >NGL
    ANIHAL NO: 3032            PATHOLOGY  ID, NO;  853032             PATHOLOGIST; DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH;                                        DAYS  ON TEST:  91
    
    REFERENCE TO  NECROPSY RECORD;           RELATED  HISTOPATHOLOGY;
    
     NGL
    ANIMAL NO: 3033            PATHOLOGY  ID. NO:  853033             PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                   .                     DAYS  ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD;           RELATED HISTOPATHOLOGY;
    
    >HISTO-AZGOS AND RT. DIAPHRAGMATIC       POORLY PERFUSED WITH  BLOOD.
     LUNG PALE IN COLOR.
    ANIMAL NO: 3034            PATHOLOGY  ID. NO: 853034             PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:   •        RELATED HISTOPATHOLOGY:
    
    >NGL
                                   (Report Continued)
                                       IV-9
    

    -------
                            PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAWLEY RATS
                    Correlation  o-f Gross &  Micro  Findings
    PROJECT  ID:  OCRESOL  /   GROUP:  0,QMS/KG    SEX:  FEMALE     DAYS: ALL
    PAGE  4               "    FATES;  ALL
    
    
    ANIMAL NO: 3035    •         PATHOLOGY ID.  NO:  853035            PATHOLOGIST;  DSC
    ANIMAL FATE:  SCHEDULED SACRIFICE
    PROBABLE  CAUSE OF  DEATH:              '         "                DAYS CM TEST: 93
    
    REFERENCE TO  NECROPSY  RECORD:            RELATED  HISTOPATHOLOGY:
    
    >H!STQ-RT. KIDNEY-DILATED PELUIS.         KIDNEY- HYDRONEPHROSIS
    ANIMAL NO;  3036             PATHOLOGY  ID.  NO:  853036            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    -PROBABLE  CAUSE OF  DEATH:                                        DAYS ON TEST: 93
    
    REFERENCE TO  NECROPSY RECORD:           RELATED HISTOPATHOLOGYt
    
     NGL
    ANIMAL NO; 3037             PATHOLOGY  ID,  NOs  853037            PATHOLOGIST!  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  93
    
    REFERENCE TO-NECROPSY RECORD:            RELATED HISTOPATHOLOGY;
    
    )NGL
    ANIMAL NO: 3038             PATHOLOGY  ID. NO:  853038            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                       -; DAYS ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
                                   (Report  Continued)
                                        IV-10
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       QRTHQ-CRE30L
                                    STUDY NO.  5221.06
                                   SPP.AGUE-DAULEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT ID: OCRESOL      GROUP:  0.OMG/KG     SEX:  FEMALE     DAYS:  ALL
    PAGE 5              -"    FATES:  ALL
    
    
    ANIMAL NO: 3039             PATHOLOGY  ID.  NO:  853039            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:                       •                DAYS ON TEST; 92
    
    REFERENCE TO NECROPSY RECORD!            RELATED  HISTOPATHQLQGY:
    
    >HI£TO-RT. KIDNEY-DILATED  PELVIS.         KIDNEY- HYDRONEPHROSIS
    
    >HISTO-CALCIFIED MATERIAL  FOUND IN       NO COROLLARY  CHANCE DETECTED
     BLADDER.
    ANIMAL NO: 3040             PATHOLOGY  10.  NO:  853040             PATHOLOGIST:  DSC
    ANIMAL FATE; SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST-. 93
    
    . EFERENCE T0 NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3041            PATHOLOGY  ID. NO:  853041             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST'. 93
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHDLOGY:
    
    >NGL
                                   (Report  Continued)
                                        IV-11
    

    -------
                                       ORTHO-CRE30L
                                    STUDY NO.  5221,06
                                   SPRAGUE-OAWLEY RATS
                    Correlation  of Gross &  Micro Findings
    PROJECT ID; OCRESOL      GROUP:  O.OMG/KG    SEX:  FEMALE     DAYS: ALL
    PAGE 6              -    FATES:  ALL
    
    
    ANIMAL NO: 3042        •     PATHOLOGY 10.  NO:  853042            PATHOLOGIST! DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF  DEATH:                       "                DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLQGY;
    
    >NGL
                                   (End  o-f  Riport)
                                        IV-12
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                   STUDY NO.  5221.06
                                  SPRAGUE-DAULEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT ID: OCRESOL     GROUP: 50 MS. KG   - 'SEX: MALE        DAYS: ALL
    PACE 1               •   FATES: ALL
    
    
    ANIMAL NO: 2924            PATHOLOGY ID. NO: 852924            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >KIDNEY-SLIGHTLY MOTTLED.                NO  COROLLARY  CHANGE  DETECTED
    ANIMAL NQ5 2925            PATHOLOGY  ID, NO:  852925             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST:  92
    
     .EFERENCE TO NECROPSY RECORDS           RELATED HISTOPATHOLOGY5
    
    >NGL
    ANIMAL NO: 2926   '         PATHOLOGY ID. NO: 852926            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS  ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL MO: 2927            PATHOLOGY ID. NO: 852927            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                           '            DAYS  ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
                                       1V-13
                                  (Report Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO,  5221 ,06
                                   SPRAGUE-DAWLEY RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL  •    GROUP:  50  MG.KG     SEX:  MALE        DAYSj  ALL
    PAGE  2                   FATES:  ALL
    
    
    ANIMAL NO: 2928             PATHOLOGY  ID.  NO:  85,2923             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                                        DAYS ON  TEST:  92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGYi
    
    >NGL
    ANIMAL NO: 2929            PATHOLOGY  ID, NO:  85292?             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS  ON  TEST:  91
                                                                      y
    
    REFERENCE TO  NECROPSY RECORD:           RELATED  HISTOPATHQLQGY:
    
     _T. KIDNEY-PELVIS DILATED,              KIDNEY- HYDRONEPHROSIS
    ANIMAL NO: 293G             PATHOLOGY  ID. NO:  852930             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                         '               DAYS  ON  TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGYs
    
    >KIDNEYS-SL!GHTLY MOTTLED.               NO  COROLLARY  CHANGE  DETECTED
    
    >TESTES-SMALL                            TESTES- ATROPHY, SEMINIFEROUS  TUBULE
    ANIMAL NO: 2931            PATHOLOGY  ID. NO:  852931             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >KIDMEYS-SLIGHTLY MOTTLED AND PITTED.    KIDNEY- NEPHROPATHY,  CHRONIC
                                        IV-14
                                   (Report  Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       QRTHQ-CRESQL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAWLEY RATS
                    Correlation  o-f Gross &  Micro  Findings
    PROJECT  ID;  OCRESOL -    GROUP;  50  MS.KG    SEX:  MALE       DAYS:  ALL
    PAGE 3                   FATES:  ALL
    
    
    ANIMAL NO; 2932             PATHOLOGY ID,  NO:  852932            PATHOLOGIST:  DSC
    ANIMAL FATE;  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH;                   •                     DAYS ON TEST: 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NQL
    ANIMAL NO: 2933    .         PATHOLOGY ID,  NO:  852933             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST; 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
     NGL
    ANIMAL NO: 2934             PATHOLOGY  ID.  NO:  852934             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                  -                      DAYS ON TEST; 92
    
    REFERENCE TO NECROPSY RECORD!            RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO; 2935            PATHOLOGY  ID.  NO:  852935             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST; 92
    
    REFERENCE TO NECROPSY RECORD:            RELATED HISTOPATHOLOGY;
    
    >NGL
                                        IV-15
                                   (Report  Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC,
    
                                       ORTHO-CRESQL
                                    STUDY  NO.  5221.06
                                   3PRAGUE-DAUILEY RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL -    GROUP: 50 MG.KG     SEX:  MALE        DAYS:  ALL
    PAGE  4              '    FATES! ALL
    
    
    ANIMAL NO; 2936            PATHOLOGY  ID, NO:  352936             PATHOLOGIST;  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON  TEST;  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2937            PATHOLOGY  ID. NOt  352937             PATHOLOGIST!  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
     NGL
    ANIMAL NO: 2938            PATHOLOGY  ID. NO:  852938             PATHOLOGIST:  DSC
    ANIMAL FATE; SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL MO: 2939            PATHOLOGY  ID. NO:  852939             PATHOLOGIST?  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
                                  (Report Continued)
                                        IV-16
    

    -------
                           PATHOLOGY ASSOUiA'l ES ,  AINU.
    
                                       ORTHO-CRESOL.
                                    STUDY NO. 5221,06
                                   SPRAGUE-OAWLEY RATS
                    Correlation  o-f Gross &•  Micro  Findings.
    PROJECT  ID;  OCRESOL      GROUP:  50 MG.KG    SEX:  MALE       DAYS: ALL
    PAGE  5               '    FATES;  ALL
    
    
    ANIMAL NO: 2940             PATHOLOGY ID.  NO:  352940            PATHOLOGIST: DSC
    ANIMAL FATE:  SCHEDULED SACRIFICE
    PROBABLE  CAUSE  OF  DEATH:                                        DAYS ON TEST; 92
    
    REFERENCE TO  NECROPSY  RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO;  2941             PATHOLOGY ID.  NO:  852941             PATHOLOGIST: DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE  OF  DEATH;                                        DAYS ON TEST; 93
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    ANIMAL NO: 2942             PATHOLOGY  ID.  NO:  852942            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2943             PATHOLOGY  ID,  NO:  852943            PATHOLOGIST: DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                       ' DAYS ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
    >NGL
                                   (End  o-f  Report)
                                        IV-17
    

    -------
                           PATHOLOGY  ASSOCIATES,  INC.
    
                                      QRTHO-CRESOL
                                   STUDY NO.' 5221 .06
                                  SPRAGUE-OAULEY  RATS
                    Correlation of  Gross  & Micro Findings
    PROJECT ID; OCRESOL     GROUP: 50 MG/KG    SEXr FEMALE     DAYS: ALL
    PAGE i                  FATES: ALL
    
    
    ANIMAL NO: 3054            PATHOLOGY ID. NO: 353056            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 91,
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3057       .     PATHOLOGY ID. NO: 853057            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST 5 92
     ;EFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3058            PATHOLOGY ID. NO: 853058            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3059            PATHOLOGY ID. NO! 853059           ' PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
                                       IV-18
                                  (Report Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESQL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAWLEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  10: OCRESOL      GROUP:  50  MG/KG     SEX:  FEMALE     DAYS:  ALL
    PAGE  2                   FATES;  ALL
    
    
    ANIMAL MO: 3060            PATHOLOGY  ID.  NO:  853060             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3041            PATHOLOGY  ID, NO:  853061             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    ANIMAL NO: 30NGL
    ANIMAL NO: 3063            PATHOLOGY  ID. NO:  8S3063            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >RT. KIDNEY-PELVIS DILATED,               KIDNEY- HYDRONEPHROSIS
                                   
    -------
                            PATHOLOGY  ASSOCIATES,  INC
    
                                       ORTHO-CRESGL
                                    STUDY NO. 5221.06
                                   SPRAGUE-DAWLEY RATS
                     Correlation  o-f Gross &  Micro Findings
     PROJECT ID;  OCRESOL     GROUP: 50 MG/KG    SEX; FEMALE     DAYS; ALL
    .PAGE 3              '    FATES: ALL
    
    
     ANIMAL NO:  3064.            PATHOLOGY ID. NO;  853064           ' PATHOLOGIST: DSC
     ANIMAL FATE:  SCHEDULED SACRIFICE
     PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 92
    
     REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
     >NGL
    ANIMAL NO:  3065            PATHOLOGY ID.  NO:  853065            PATHOLOGIST: DSC
    ANIMAL FATE:  SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH;                                        DAYS ON TEST: 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
      NGL
    ANIMAL  NO:  3046             PATHOLOGY ID.  NO:  853066            PATHOLOGIST: DSC
    ANIMAL  FATE:  SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 93
    
    REFERENCE TO  NECROPSY  RECORD:            RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL  NO:  3067             PATHOLOGY ID.  NO:  853067            PATHOLOGIST: DSC
    ANIMAL  FATE:  SCHEDULED SACRIFICE
    PROBABLE  CAUSE OF DEATH:                                       ~~ DAYS ON TEST: 93
    
    REFERENCE TO  NECROPSY  RECORD:            RELATED HISTOPATHOLOGY:
    
    >N6L
                                   {Report Continued)
                                        IV-2Q
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAWLEY  RATS
                    Correlation  o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL •     GROUP:  50  MG/KG     SEX:  FEMALE      DAYS:  ALL
    PAGE  4                   FATES:  ALL
    
    
    ANIMAL NO: 3063             PATHOLOGY  ID. NO:  853068             PATHOLOGIST;  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS  ON  TEST:  93
    
    REFERENCE TO  NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3069            PATHOLOGY  ID. NO: 853049             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH!                                        DAYS  ON  TEST:  93
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLQGY:
    
     NGL
    ANIMAL NO: 3070            PATHOLOGY  ID. NO: 853070             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                 .       DAYS  ON  TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3071            PATHOLOGY  ID. NO: 853071             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATHs                                        DAYS  ON  TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOOY:
    
    >NGL
                                   (Report Continued)
                                        IV-21
    

    -------
                            PATHOLOGY ASSOCIATES,  INC.
    
                                       QRTHO-CRESOL
                                    STUDY NO. 5221.0*
                                   SPRAGUE-DAWLEY RATS
                    Correlation  o-f Gross &  M'icro Findings
    PROJECT  ID:  OCRESOL     GROUP:  50 MG/KG    SEX; FEMALE     DAYS: ALL
    PAGE  5               "    FATES:  ALL
    
    
    ANIMAL NO:  3072             PATHOLOGY ID.  NO:  853072            PATHOLGSIST: DSC
    ANIMAL FATE:  SCHEDULED SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                        "                DAYS ON TEST:. 92
    
    REFERENCE TO  NECROPSY  RECORD:            RELATED HISTQPATHQLOGY:
    
    >NGL
    ANIMAL NO: 3073             PATHOLOGY ID.  NO:  853073            PATHOLOGIST: DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                              •          DAYS ON TEST: 93
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    ANIMAL NO: 3074             PATHOLOGY ID.  NO s  853074            PATHOLOGIST: DSC
    ANIMAL FATEs SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TESTi 93
    
    REFERENCE TO NECROPSY RECORD;            RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL MO: 3075             PATHOLOGY  ID.  MO:  853075            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                      -• DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
                                                                                     I
    >NGL                                                 '                            I
                                   (End  o*  Report)
                                        IV-22
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESQL
                                    STUDY MO.  5221.06
                                   SPRAGUE-DAULEY  RATS
                    Correlation o-f  Gross &. Micro  Findings
    PROJECT  ID: OCRESOL     GROUP:  175MG/KG     SEX:'HALE       DAYS:  ALL
    PAGE  1                  FATES:  ALL
    
    
    ANIMAL NO: 2957             PATHOLOGY  ID.  NO:  852957            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    -PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 9Z
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOQY;
    
    >NGL
    ANIMAL NO: 2958            PATHOLOGY  ID. NO:  85295B            PATHOLOGIST:  DSC
    ANIMAL FATEJ SCHEDULED SACRIFICE                                                ;
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST:  92-
    
     .EFERENCE TO NECROPSY RECORDi            RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NOs 2959            PATHOLOGY  ID. NO:  852959             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                              '          DAYS ON TESTs 91
    
    REFERENCE TO NECROPSY RECORD!           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NOi 2960            PATHOLOGY  ID. NO:  B529cSO           '  PATHOLOGIST:  DSC
    ANIMAL FATE; SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST! 91
    
    REFERENCE TO NECROPSY RECORD;           RELATED  HISTOPATHOLOGY:
    
    >NGL
                                        IV-23
                                  (Report Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       QRTHO-CRESOL
                                    STUDY NO.  522!,06
                                   SPRAGUE-DAULEY RATS
                    Correlation  o-f  Gross & Micro  Firidings
    PROJECT  ID:  OCRESOL      GROUP:  175MG/KQ    SEX:  MALE       DAYS:  ALL
    PAGE  2               "    FATES:  ALL
    
    
    ANIMAL NO: 2961             PATHOLOGY  ID,  NO:  852961             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                       "                DAYS ON TEST;  91
    
    REFERENCE TO NECROPSY RECORD:           .RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL ND: 2962             PATHOLOGY  ID.  NO:  352962             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH;                                        DAYS  ON  TEST:  92
    
    REFERENCE TO  NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
      4GL
    ANIMAL NO: 2963            PATHOLOGY  ID. NO:  852963             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST.-  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2964            PATHOLOGY  ID. NO:  852964             PATHOLOGIST.-  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                        .              --' DAYS ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY!
    
    >NGL
                                   (Report Continued)
                                            IV-24
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.0*
                                   SPRAGUE-DAWLEY RATS
                    Correlation  o-f Oross & Micro  Findings
    PROJECT  ID:  OCRESOL      CROUP:  175MG/KG     SEX:  MALE       DAYS:  ALL
    PAGE  3                   FATES!  ALL
    
    
    ANIMAL MO: 2965             PATHOLOGY  ID.  MO:  852?o5             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO  NECROPSY RECORD:    -        RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO! 2966             PATHOLOGY  ID. NO I  352966             PATHOLOGIST;  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHQLOGY:
    ANIMAL NO: 2967            PATHOLOGY  ID, NO:  8S2967             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH!                                        DAYS ON TEST:  93
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2968            PATHOLOGY  ID. NO:  852968             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH!                                      -  DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           P.ELATED  HI STOPATHOLOGY:
    
    >NGL
                                   (Report  Continued)
                                        IV-25
    

    -------
                           PATHOLOGY ASSOCIATES',  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAULEY RATS
                    Correlation  o-f Gross &  Micro  Findings
    PROJECT  ID:  OCRESOL      GROUP:  17SM6/KO    SEX;  MALE       DAYS:  ALL
    PAGE  4               '    FATES:  ALL
    
    
    ANIMAL NO:  2969             PATHOLOGY ID.  NO:  35296?            PATHOLOGIST: DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                       "                DAYS ON TEST:  91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO:  2970             PATHOLOGY  ID.  NO:  852970             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATHJ                                        DAYS ON TEST.- 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
     NGL
    ANIMAL NO: 2971            PATHOLOGY  ID. NO;  852971             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >KIDNEY3-MOTTLED                         KIDNEY- NEPHRQPATHY,  CHRONIC
    ANIMAL NO: 2972            PATHOLOGY  ID,  NO:  852972            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                      -' DAYS ON TEST:  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
                                   (Report  Continued)
                                        IV-26
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY  NO.  5221 ,Q6
                                   SPRAQUE-OAULEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID:  OCRESQL  .    GROUP:  175MC/KG     SEX:  MALE        DAYS: ALL
    PAGE  5                   FATES:  ALL
    
    
    ANIMAL NO: 2973            PATHOLOGY  ID.  NO:  352973             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED SACRIFICE
    PROBABLE  CAUSE OF  DEATH;                   .                     DAYS ON  TEST:  9:
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLQGY:
    
    >PANCREAS-NODULE 4X3X1MM., TAN,           MESENTERY-FAT NECROSIS
     ATTACHED TO  HESENTERIC  FAT
    ANIMAL NO: 2974            PATHOLOGY  ID, NOs  852974            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:      .                                 DAYS  ON  TEST:  93
    
    DEFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY;
    
    /N6L
    ANIMAL NO: 2975            PATHOLOGY  ID. NO:  852975            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS  ON  TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2976            PATHOLOGY  ID, NO:  852976            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS  ON  TEST;  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
                                       IV-27
                                   (End of  Report)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHQ-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUG-DAWLEY  RATS
                    Correlation  o-f Gross & Micro  Findings
    PROJECT  ID: OCRE30L      GROUP:  175MG/KG     SEX:- FEMALE     DAYS; ALL
    PAGE  I                   FATES:  ALL
    
    
    ANIMAL NO: 3039             PATHOLOGY  ID.  NO:  85303?            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY5
    
    >NGL
    ANIMAL NO; 3090             PATHOLOGY  ID.  NO:  853090             PATHOLOGIST:  DSC'
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH!                                        DAYS ON TEST: 92
    
     'EFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NOs 3091            PATHOLOGY  ID.  NO:  853091             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOQY:
    
    >NGL
    ANIMAL NO: 3092            PATHOLOGY  ID. NO:  853092           -" PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS GN TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTCPATHCLOGY:
    
    >NGL
                                        IV-28
                                   (Report Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAULEY RATS
                    Correlation  o-f  Sross & Micro  Findings
    PROJECT  ID:  OCRESOL      GROUP;  175MG/KQ    SEX:  FEMALE     DAYS;  ALL
    PAGE  2              '     FATES:  ALL
    
    
    ANIMAL NO:  30?3             PATHOLOGY  10.  MO:  853093            PATHOLOGIST:  DSC
    ANIMAL FATE;  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                       *   .              DAYS ON TEST; 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3094             PATHOLOGY  ID.  NO:  853094             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
     NGL
    ANIMAL NO: 3095             PATHOLOGY  ID. NO:  853095             PATHOLOGIST:  DSC
    ANIMAL FATE.- SCHEDULED SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY;
    
    >NGL
    ANIMAL NO: 3096            PATHOLOGY  ID. NO:  853096             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                      •'" DAYS ON TEST:- 91
    
    REFERENCE TO NECROPSY RECORD:          - RELATED  HISTOPATHOLOGY:
    
    >NGL
                                   (Report  Continued).
                                        IV-29
    

    -------
                           PATHOLOGY ASSOCIATE1!
                                       ORTHO-CRES
                                    STUDY NO.  52;
                                   SPRAGUE-DAULE'i
                    Correlation  o-F Gross & Micro  Findings
    PROJECT  ID:  OCRESOL
    PAGE  3
    GROUP! 175MG/KG
    FATES: ALL
    SEX:  FEMALE
    DAYS: ALL
    ANIMAL NO: 3097             PATHOLOGY ID.  NO:  853097
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:
    REFERENCE TO NECROPSY  RECORD:
    
    >KIDNEYS-BILATERAL  PELVIS  DILATION.
                                           PATHOLOGIST: DS
    
                                           DAYS ON TEST: 9
                    RELATED HISTOPATHOLQGY:
    
                     KIDNEY- HYDRCNEPHROSIS
    ANIMAL NO: 3098             PATHOLOGY  ID.  NO:  853098
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:
                                           PATHOLOGIST: DS
    
                                           DAYS ON TEST: 9
    REFERENCE TO NECROPSY RECORDi
    
    >NGL
                    RELATED HISTOPATHOLOGYs
    ANIMAL NO: 3099             PATHOLOGY  ID. NO:  853099
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:
                                           PATHOLOGIST: DS
    
                                           DAYS ON TEST: 9
    REFERENCE TO NECROPSY RECORD:
    
    >NGL
                    RELATED HISTOPATHOLOGY:
    ANIMAL NO:- 3100            PATHOLOGY  ID, NO•, 8531 GO
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:
                                           PATHOLOGIST: DS<
    
                                           DAYS ON TEST: 9
    REFERENCE TO NECROPSY RECORD:
    
    >NGL
                    RELATED HISTOPATHOLOGY:
                                   (Report Continued)
                                       IV-30
    

    -------
                           PA i riU-Luur ASSOCIATES,  INC.
    
                                       ORTHQ-CRESOL
                                    STUDY NO.  5221 .06
                                   SPRAGUE-DAWLEY RATS
                    Correlation  of  Gross & Micro  Findings
    PROJECT  ID;  OCRESCL      GROUP;  175MG/KG    SEX:  FEMALE     DAYS;  ALL
    PAGE  4              -     FATES:  ALL
    
    
    ANIMAL NO: 3101             PATHOLOGY  ID.  NO:  853101             PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE  OF  DEATH:                       "                 DAYS ON TEST: 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    )NGL
    ANIMAL NO: 3102             PATHOLOGY  ID,  NO:  853102             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TESTs 93
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHQLOGY:
    
    SNGL
    ANIMAL NO: 3103            PATHOLOGY  ID. NO:  853103             PATHOLOGIST!  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:     •                                   DAYS ON TEST: 93
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3104            PATHOLOGY  ID. NO:  853104             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH!                                      ; DAYS ON TEST;  92
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NSL
                                   (Report  Continued")
                                        IV-31
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       QRTHO-CRESOL
                                    STUDY NO.  5221 ,06
                                   SPRAGUE-DAULEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL      GROUP:  I75MG/KG     SEX.-  FEMALE      DAYS:  ALL
    PAGE  5               •    FATES:  ALL
    
    
    ANIMAL NO: 3105             PATHOLOGY  ID, NO:  853105             PATHOLOGIST!  DSC
    ANIMAL FATE;  SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                       "                DAYS ON TEST; 91
    
    REFERENCE TO  NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3106            PATHOLOGY  ID. MO: 853106            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF DEATH:               '                        DAYS  ON TEST: 91
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
     MGL
    ANIMAL NO: 3107            PATHOLOGY  ID. NO: 853107            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                       DAYS  ON TEST; 93
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3108            PATHOLOGY  ID. NO: 353108            PATHOLOGIST; DSC
    ANIMAL FATE; SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                      ; DAYS  ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD!           RELATED HISTOPATHOLOGY:
    
    >NGL
                                  (End of Report)
                                       1V-32
    

    -------
                           PATHOLOGY  ASSOCIATES, INC
    
                                       ORTHO-CRESOL
                                   STUDY NO.  5221,06
                                  SPRAGUE-DAWLEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT ID: QCRESQL     GROUP;  60QMG/K6     SEX:. MALE        DAYS: ALL
    PAGE  1                  FATES:  ALL
    
    
    ANIMAL NO; 2934            PATHOLOGY  ID. NO:  852934             PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST]  17
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >LIYER-MOTTLED AND DARK                  LIVER- CONGESTION
    
    >INTESTINES-DARK                         AUTOLYSIS; MILD
    
    >LUNG-LEFT LOBE DARK RED                 LUNG-  CONGESTION;  NO  INFLAMMATION
                                             ASSOCIATED WITH  BACTERIA
    
    >TRACHEA-HAS OIL IN IT                   NO COROLLARY  CHANCE DETECTED
    
                                             ALL  TISSUES MILD TO MODERATE
                                             AUTOLYSIS
    ANIMAL NO: 2990            PATHOLOGY  ID. NO;  852990             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOOY:
    
    >NGL
    ANIMAL NO: 2991            PATHOLOGY  ID, NO: 852991             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY;
    
    >NGL
                                        IV-33
                                  (Report Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       QRTHO-CRESQL
                                    STUDY NO.  5221.Oi
                                   SPRAGUE-DAULEY RATS
                    Correlation a-f  Gross &  Micro  Findings
    PROJECT  ID: QCRESOL  .    GROUP:  4QQMG/KG    SEX:  MALE       DAYS: ALL
    PAGE 2       '            FATES:  ALL
    
    
    ANIMAL NO: 2992             PATHOLOGY ID.  NO:  852992            PATHOLOGIST: DSC
    ANIHAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                         DAYS ON TEST: 2
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHQLGGY:
    
    >LUNGS-MDTTLED                            LUNG- CONGESTION
    
    >LIVER-DARK'RED                           LIVER-  CONGESTION
    ANIMAL NO: 2993             PATHOLOGY ID.  NOs  852993            PATHOLOGIST: DSC
    ANIMAL FATE: FOUND  DEAD
    PROBABLE CAUSE OF DEATH:                                         DAYS ON TEST: 9
    
     EFERENCE TO NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
    XTISSUE PARTIALLY   AUTOLYZED;  NVL
    
    >                           -              TISSUES MILDLY AUTOLYTIC, MAMMARY
                                              GLAND ASSOCIATED WITH MUSCLE
                                              SPECIMEN
    ANIMAL NO: 2994             PATHOLOGY ID.  NO:  852994            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF  DEATH:                         .               DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:            RELATED HISTQPATHQLQGY.
    
    >NGL
                                   (Report  Continued)
                                        IV-34
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       CRTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAWLEY RATS
                    Correlation o-F  Gross &. Micro  Findings
    PROJECT ID: OCRESOL     GROUP:  400MG/KO     SEX:  MALE       DAYS:  ALL
    PABE 3               '   FATES:  ALL
    
    
    ANIMAL NO; 2995             PATHOLOGY  ID.  NO:  352995            PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH;                       "                DAYS ON TEST:  35
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >LUNGS-MOTTLED RED                        LUNG- CONGESTION;  PRESENCE OF OIL
                                              DROPLET IN LUNGS SUGGESTS
                                              INHALATION. LYMPHQCYTIC  CUFFS IN
                                              LUNG INCLUDED  PLASMA CELLS.
    ANIMAL NO; 2996            PATHOLOGY  ID.  NO;  852996            PATHOLOGIST:  DSC
    ANIMAL FATE; SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH-,                                        DAYS ON TEST:  91
    
     .EFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2997            PATHOLOGY  ID. NO:  852997            PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 18
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >OIL IN TRACHEA                          MO COROLLARY CHANGE DETECTED; NO
                                             EVIDENCE  OF OIL IN LUNG
                                   (Report  Continued)
                                        IV-35
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  522i.06
                                   SPRAGUE-DAULEY RATS
                    Correlation o-f  Gross &. Micro  Findings
    PROJECT  ID:  OCRE30L      GROUP:  dCOMG/KG    SEX:  MALE       DAYS:  ALL
    PAGE  4               "    FATES:  ALL
    
    
    ANIMAL NO: 2998   •          PATHOLOGY ID.  NO:  852998            PATHOLOGIST; DSC
    ANIMAL FATE;  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                                        DAYS ON TEST; 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 2999             PATHOLOGY  ID.  MO 5  852999            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH;                                        DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY;
    
      JGL
    ANIMAL NO: 3000             PATHOLOGY  ID.  NO:  353000             PATHOLOGIST!  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST; 64
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY;
    
    >LUNGS-RED MOTTLED,  INFLATED              LUNG- CONGESTION
    
    >NASAL CAVITY-OIL                         NO  COROLLARY CHANGE DETECTED
    
    >ESOPHAGUS & STOMACH-SMALL  AMOUNT  OF      NO  COROLLARY CHANGE DETECTED
     OIL
                                   (Report  Continued)
                                        IV-36
    

    -------
                              I HUL.UU'»  rti>isUl_i A l"tS ,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5£Z:,06
                                   SPRAGUE-DAWLEY  RATS
                    Correlation of  Gross & Micro  Findings
    PROJECT  ID;  OCRESOL      GROUP:  60QMG/KG     SEX:  MALE       DAYS:  ALL
    PAGE  5                   FATES:  ALL
    
    
    ANIMAL NO: 3001             PATHOLOGY  ID.  MO:  853001             PATHOLOGIST;  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE CAUSE  OF  DEATH:                        "                DAYS ON TEST;  92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
    >NGL
    
    >                                         INFLAHMATIONCGRANULQMATOUS) IS IN
                                              C.T.  ASSOCIATED WITH THYROID AND
                                              CONTAINS FOREIGN-BODY  GIANT CELLS
    ANIMAL NO: 3002            PATHOLOGY  ID.  NO:  853002            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
     ^QSABLE CAUSE OF DEATH:                                        DAYS ON TEST:  93
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3003            PATHOLOGY  ID. NO:  853003             PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NCL
                                   (Report  Continued)
                                        IV-37
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY  NO.  5221.06
                                   SPRAGUE-DAWLEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: QCRESQL     GROUP:  600MG/K6     SEX:  MALE       DAYS:  ALL
    PAGE 6               '   FATES:  ALL
    
    
    ANIMAL MO: 3004            PATHOLOGY  ID. MO:  353004             PATHOLOGIST:  OSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH;                            .             DAYS ON TEST:  2
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY!
    
    >NGL
    
    >  •                                      TISSUES-MILD  AUTQLYSIS
    ANIMAL NO: 3005            PATHOLOGY  ID. NO:  653005'            PATHOLOGIST;  DSC
    ANIMAL FATE: SCHEDULED SACRIFICE
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST:  92
    
     EFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:
    
    >NOL
    ANIMAL NO: 3006            PATHOLOGY  ID. NO:  853006             PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:              -                    .      DAYS ON TEST:  46
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTQPATHOLOGY:
    
    >MOUTH & NOSE-OIL AROUND THEM            NO  COROLLARY  CHANGE  DETECTED
    
    >LUNGS-MOTTLED RED                       LUNG- CONGESTION
    
    >SPLEEN- ONE HALF DISCOLORED, BLACK      AUTOLYSIS-MODERATE
    
    >                                        ALL  TISSUES MILD TO  MODERATE
                                             AUTOLYSIS
                                  (Report'Con tinued)
    
                                        IV-38
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESDL
                                    STUOY NO. 5221,06
                                   SPRAGUE-DAWLEY RATS
                    Correlation  o-f Gross. &  Micro Findings
    PROJECT  ID;  OCR.ESOL     GROUP;  6QOMG/K3    SEX: MALE       DAYS; ALL
    PAGE  7                   FATES:  ALL
    
    
    ANIMAL NO: 3007             PATHOLOGY ID.  NO: 853007            PATHOLOGIST; DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                        "                DAYS ON TEST: 92
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLQGY:
    
    >KIDNEYS-SLIGHTLY  MOTTLED                 NO COROLLARY CHANGE DETECTED
    ANIMAL NO:  3003             PATHOLOGY ID.  NO: 853008            PATHOLOGIST: DSC
    ANIMAL FATE: FOUND  DEAD
    PROBABLE CAUSE OF DEATH:                                         DAYS ON TESTs 9
    
    REFERENCE TO NECROPSY  RECORD:            RELATED HISTOPATHOLOGY:
    
     NGL
    ANIMAL NO: 3009             PATHOLOGY ID.  NO:  853009            PATHOLOGIST: DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 92
    
    REFERENCE TO NECROPSY RECORDS            RELATED HISTOPATHOLOGYs
    
    >NGL
                                   
    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       OR7HO-CRESOL
                                    STUDY NO,  5221.06
                                   SPRAGUE-DAWLEY RATS
                    Correlation  o-f Gross &  Micro  Findings
    PROJECT  ID:  OCRESOL      GROUP;  60QMG/KG    SEX:  FEMALE     DAYS: ALL
    PACE  1          •         FATES:  ALL
    
    
    ANIMAL NO: 3112             PATHOLOGY ID.  NO:  353112    '        PATHOLOGIST: DSC'
    ANIMAL FATE:  FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS DM TEST: 16'
    
    REFERENCE TO  NECROPSY  RECORD:    .        RELATED  HISTOPATHOLOQY:
    
    >LUNGS DARK  RED, FIRM,  AND FAILED TO     LUNG- CONGESTION, LUNG- EDEMA
     COLLAPSE
    
    >0!L  IN TRACHEA                           NO COROLLARY CHANGE DETECTED.  OIL
                                              DROPLET IN LUNGS SUGGESTS
                                              ASPIRATION,
    ANIMAL NO:  3113             PATHOLOGY ID.  NO:  853113            PATHOLOGIST: DSC
    ANIMAL FATE; FOUND  DEAD
    PROBABLE CAUSE OF  DEATH:                                        DAYS ON TEST: 35
    
    REFERENCE TO NECROPSY  RECORD:            RELATED HISTOPATHOLOGY:
    
    >MESENTERY-NECROSIS FAT,  5X5MM           NECROTIC FAT NOTED AT TRIM IS
     BROWN; DETECTED AT TRIM                  AUTOLYTIC PANCREATIC LN, MESENTERIC
                                              FAT,  AND PANCREAS UJITH A SMALL
                                              AMOUNT OF NECROTIC FAT SURROUNDING.
    
    >                                         ALL  TISSUES ARE MILDLY TO
                                              MODERATELY AUTOLYTIC.
    ANIMAL NO: 3121             PATHOLOGY ID.  NOs  853121            " PATHOLOGIST: DSC
    ANIMAL FATE: FOUND  DEAD
    PROBABLE CAUSE  OF DEATH:                               '          DAYS ON TEST: 0
    
    REFERENCE TO NECROPSY  RECORD:            RELATED HISTOPATHOLOGY:
    
    >LUNGS-MOTTLED-ALL  LOBES                  LUNG- EDEMA
    
    yLIVER-DARK                               MILD AUTOLYSIS
    
    >KIDNEYS-DARK                             MILD AUTOLYSIS
    
                                        IV-40
    
                                   (Report  Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                   STUDY NO,  5221.06
                                  SPRAGUE-DAUILEY  RATS
                    Correlation o-f  Gross  & Micro Findings
    PROJECT ID; OCRESOL -    GROUP: 400MC/KG     SEX:  FEMALE     DAYS; ALL
    PAGE 2                  FATES: ALL
    
    
    ANIMAL NO: 3121            PATHOLOGY  ID. NO: 853121            PATHOLOGIST: DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST:  0
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTOPATHOLOGY:                :
    
    >                                        ALL TISSUES MILDLY AUTOLYTIC.  ALSO
                                             EVIDENCE OF ARTIFACTS DUE TC
                                             FREEZING,  PRESENCE OF OIL IN LUNG
                                             SUGGESTS INHALATION.
    ANIMAL NO: 3122     .       PATHOLOGY ID. NOs 853122            PATHOLOGIST: OSC
    ANIMAL FATE: FOUND DEAD
    CROBABLE CAUSE OF DEATH:                                       DAYS ON TEST:  18
    
    REFERENCE TO NECROPSY RECORD:  .         RELATED HISTOPATHOLOGY!
    
    >LUNGS-RED, MOTTLED.         '            LUNG- CONGESTION.  NO EVIDENCE OF
                                             OIL IN LUNG.
    ANIMAL NO; 3123        •    PATHOLOGY ID. NO: 853123            PATHOLOGIST: DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                       DAYS ON TEST:  IS
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >LUNGS-RED, MOTTLED                      LUNG- CONGESTION
    
    >MANDIBULAR LYMPH NODE-RED, RIGHT        MANDIBULAR LYMPH NODE- CONGESTION
     SIDE
                                  
    -------
                           PATHOLOGY ASSOCIATES,  JNC
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAULEY RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL      QROUP:  ^QOMG/KG     SEX:  FEMALE     DAYS:  ALL
    PAGE 3               '    FATES:  ALL
    
    ANIMAL NO: 3124             PATHOLOGY  ID.  MQ;  853124        '    PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:              .                          DAYS ON TEST:  33
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >NGL
    
    >                                         ALL  TISSUES MILD TO MODERATE
                                              AUTOLYSIS
    ANIMAL NO: 3125             PATHOLOGY  ID.  NO:  8S3125            PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                     '                   DAYS ON TEST: 35
    
     >EFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOQY:
    
    >NQL
    
    >                                         TISSUES MILDLY TO MODERATELY
                                              AUTOLYTIC.
    ANIMAL NO: 3126            PATHOLOGY  ID.  NO:  853126             PATHOLOGIST:  DSC
    ANIMAL FATES FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 32
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >OIL FLOWED FROM TRACHEA                  NO  COROLLARY  CHANGE DETECTED
    
    >LUNGS-RED AND MOTTLED                   ' LUNG- CONGESTION,   NO REACTION
                                              (INFLAMMATION,  ETC.)  ASSOCIATED
                                              WITH BACTERIA IN  L-Jwl5
    
    >LIMER-DARK RED                           LIUER-  CONGESTION
    
    ^INTESTINES STARTED TO FORM  OAS           AUTOLYTIC CHANGE,  MILD
                                   (Report  Continued)
                                            IV -42
    

    -------
                           PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESOL
                                    STUDY  MO.  5221,06
                                   SPRAGUE-DAULEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRESOL      GROUP:  600H6/KG     SEX;  FEMALE      DAYS:  ALL
    PAGE 4                   FATES:  ALL
    
    
    ANIMAL NO; 3126             PATHOLOGY  ID. NO:  853126             PATHOLOGIST;  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON TEST:  3;
    
    REFERENCE TO NECROPSY  RECORD:            RELATED  HISTOPATHOLOGY:
    
    >RED STAIN-NOSE                          INTESTINE-DISTENDED WITH GAS            MILD AUTOLYSIS
    
    >STOMACH-DISTENDED WITH GAS       .      MILD AUTOLYSIS
    ANIMAL NO: 3128            PATHOLOGY  ID. NO:  853128             PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  B9
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGY:
    
    >JEJUNUM AND ILEUM ARE RED               MILD AUTOLYSIS
    
    >HEART SLIGHTLY ENLARGED                 NO COROLLARY  CHANGE  DETECTED
    
    >LUNGS MOTTLED                           LUNG- CONGESTION.  NO  EVIDENCE OF
                                             OIL  IN LUNG
                                   (Report  Continued)
    
                                        IV-43
    

    -------
                            PATHOLOGY ASSOCIATES,  INC
    
                                       ORTHO-CRESQL
                                    STUDY NO. 5221 ,06
                                   SPRABUE-DAWLEY RATS
                    Correlation  o-f Gross &  Micro Findings
    PROJECT  ID;  OCRESOL      GROUP;  600HG/KG   -SEX: FEMALE     DAYS; ALL
    PAGE  5               "    FATES:  ALL
    
    
    ANIMAL NO':  3129             PATHOLOGY ID.  NO: 853129            PATHOLOGIST: DSC
    ANIMAL FATE:  FOUND  DEAD
    PROBABLE  CAUSE OF DEATH:                                        DAYS ON TEST: 91
    
    REFERENCE TO  NECROPSY  RECORD:            RELATED HISTQPATHOLOGY:
    
    >LUNGS-MOTTLED                            NO EVIDENCE OF OIL IN LUNG.   LUNG-
                                              CONGESTION
    
    >LEFT KIDNEY-ENLARGED;  PALE-PELVIS;       KIDNEY- HYDRONEPHROSIS
     MILDLY DILATED.
    ANIMAL NO: 3130             PATHOLOGY  ID,  NO:  853130     .    .   PATHOLOGIST! DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
     30BABLE CAUSE OF  DEATH;                                        DAYS ON TEST: 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
    >NGL
    ANIMAL NO: 3131             PATHOLOGY  ID.  NO:  853131             PATHOLOGIST: DSC
    ANIMAL FATE: FOUND  DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS ON TEST: 17
    
    REFERENCE TO NECROPSY RECORD:            RELATED HISTOPATHOLOGY:
    
    >ALL TISSUES APPEAR DARK                  ALL  TISSUES MILD TO MODERATE
                                              AUTQLYSIS
    
    >INTESTINE SOFT                           AUTOLYSIS
    
    >LIUER MOTTLED                            LIVER- CONGESTION
    
    >LUNGS MOTTLED                            LUNG- CONGESTION
                                   (Report  Continued)
                                        IV-44
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY NO.  5221 .06
                                   SPRAGUE-DAUJLEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT ID; OCRE30L
    PAGE 6
    GROUP: 600MG/KG
    FATES: ALL
       SEX: FEMALE
    DAYS: ALL
    ANIMAL MO: 3132
    ANIMAL FATE; FOUND DEAD
    PROBABLE CAUSE OF DEATH:
       PATHOLOGY ID. MO: 853132
    REFERENCE TO NECROPSY RECORD:
    
    >0!L AROUND NOSE
    
    >RED MOTTLED LUNGS
                           PATHOLOGIST: DSC
    
                           DAYS ON TEST: 14
    
    RELATED HISTOPATHOLOGY:
    
     MO COROLLARY CHANGE DETECTED
    
     LUNG- CONGESTION
    ANIMAL NO: 3133
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:
       PATHOLOGY ID, NO: 853133
     IFERENCE TO NECROPSY RECORD:
    
    >RED MOTTLING ON ALL LOBES OF THE
     LUNGS
                           PATHOLOGIST: DSC
    
                           DAYS ON TEST: 12
                    RELATED HISTOPATHOLOGY:
    
                     LUNS- CONGESTION.  NO EVIDENCE OF
                     OIL IN LUNG.
    ANIMAL NO: 3134
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:
       PATHOLOGY ID. NO: 853134
    REFERENCE TO NECROPSY RECORD:
    
    >TISSUES APPEAR DARK
    
    >NO OIL IN TRACHEA
    
    >INTESTINES AUTQLYZED
                           PATHOLOGIST: DSC
    
                           DAYS ON TEST: 17
    
    RELATED HISTOPATHOLOGY:
    
     MODERATE AUTOLYSIS OF TISSUES
    
     NO COROLLARY CHANGE DETECTED
    
     MODERATE AUTOLYSIS OF TISSUES
                                   (Report Continued)
                                        IV-45
    

    -------
                           rrtiHQi_UGY AobliCiATCS,  INC,
    
                                       ORTHO-CRE30L
                                    STUDY NO.  5221.06
                                   SPRAGUE-DAULEY RATS
                    Correlation  0-6  Gross &  Micro  Findings
    PROJECT  ID:  QCRESOL      GROUP:  6QOMG/KG    SEX;  FEMALE     DAYS: ALL
    PAGE  7               •    FATES:  ALL
    
    
    ANIMAL NO: 3135             PATHOLOGY ID.  NO:  853135            PATHOLOGIST:  DSC
    ANIMAL FATE:  SCHEDULED  SACRIFICE
    PROBABLE  CAUSE OF  DEATH:                                        DAYS ON TEST: 91
    
    REFERENCE TO  NECROPSY RECORD:            RELATED  HISTQPATHOLQGYs
    
    >RT.  KIDNEY-PELVIS DILATED.               NO COROLLARY CHANGE DETECTED
    ANIMAL NO: 3136             PATHOLOGY  ID.  NO:  853136            PATHOLOGIST:  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH;                                        DAYS ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTDPATHOLOGY:
    
     NGL
    ANIMAL NO: 3137             PATHOLOGY  ID. NO:  853137            PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND  DEAD
    PROBABLE CAUSE OF DEATH:                                         DAYS ON TEST:  9
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY:
    
    >ALL TISSUE PARTIALLY AUTOLYZED.         ALL  TISSUE MILD TO MODERATE
                                             AUTOLYSIS
    ANIMAL NO: 3138            PATHOLOGY  ID. NO:  853138             PATHOLOGIST;  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                     '                  '  DAYS ON TEST:  8
    
    REFERENCE TO NECROPSY RECORD:            RELATED  HISTOPATHOLOGY5
    
    >LUNG3 MOTTLED RED                       LUNG- CONGESTION
    
    ^EVIDENCE OF OIL IN THE STOMACH          NO  COROLLARY  CHANGE DETECTED
                                        IV-46
    
                                   (Report  Continued)
    

    -------
                           PATHOLOGY ASSOCIATES,  INC.
    
                                       ORTHO-CRESOL
                                    STUDY MO.  5221.06
                                   SPRAGUE-DAWLEY  RATS
                    Correlation o-f  Gross & Micro  Findings
    PROJECT  ID: OCRE30L     GROUP;  6QGMG/KG     SEX:  FEMALE      DAYS:  ALL
    PAGE 3               '   FATES:  ALL
    
    
    ANIMAL NO: 3139            PATHOLOGY  ID. NO:  B5313?             PATHOLOGIST!  DSC
    ANIMAL FATE: SCHEDULED  SACRIFICE
    PROBABLE CAUSE OF  DEATH:                                        DAYS  ON TEST:  91
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTQPATHOLQGY:
    
    >NGL
    ANIMAL NO: 3140            PATHOLOGY  ID. NO: 853140             PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  18
    
    REFERENCE TO NECROPSY RECORD:           RELATED  HISTQPATHOLQGY:
    
     3ED MOTTLED LUNGS                       LUNG- CONGESTION
    ANIMAL NOi 3141            PATHOLOGY  ID. NO; 353141             PATHOLOGIST:  DSC
    ANIMAL FATE: FOUND DEAD  -
    PROBABLE CAUSE OF DEATH:                                        DAYS  ON  TEST:  35
    
    REFERENCE TO NECROPSY RECORD:           RELATED HISTOPATHOLOGYs
    
    >NGL
    
    >                                        ALL TISSUES MILD  TO  MODERATE
                                             AUTOLYSIS.
                                   (End of Report)
                                        IV-47
    

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       2888
    
    
       2889
    
    
       2915
    
    
       2921
      2923
      2947
      2948
    
      2949
    
    
      2950
                          GROSS AND MICROSCOPIC  FINDINGS
                                    45 DAY  SACRIFICE
    Animal  No.   DflS£_fijL
    
       2881       Op. 1
    Qp. 1
    
    
    Gp. 1
    
    
    6p. 2
    
    
    Gp. 2
    Op. 2
    Gp. 3
    Qp. 3
    
    Gp.3
    
    
    Op. 3
                  MALES
    
    Gross Observation
    
    Kidney-slight mottling
    tan/red
    
    Kidneys-both pale and
    mottled
    Microscopic QbseryjtiQD
    
    No corresponding lesion
    
    
    Nephropathy, chronic, minimal
    RL and Lt Kidneys- pelvis   No corresponding lesion
    dilated
    Kidney-slightly mottled
    red/tan
    
    Liver-round, (5-7mm)
    dark tan mess, accessory
    lobe-upon incision filled
    with clotted blood
    Nephropathy, chronic, minimal
    
    
    Infarct, accessory lobe, severe
                             Lumbar LN-enlarged        Hemorrhage, acute, mild
    
                             Kidneys-mottled red/tan     No corresponding lesion
    Kidneys-pale, brown
    Nephropathy, chronic, minimal
    Prostate-rt. lobe-enlarged   Normal secretion dilates the gland.
                              Dilation, glands, mild
    
    Kidney-darken flat foci      No corresponding lesion
    (Less than or equal to ,3mm)
    (barely perceivable) on
    cortical surface. Both
    kidneys pale.
    Kidneys-pale
    
    Kidneys-both pale and
    mottled
    
    Kidneys-botn pale and
    mottled, red and tan
    No corresponding lesion
    
    Nephropathy, chronic, minimal
    
    
    No corresponding lesion
                                          IV-48
    

    -------
                         GROSS AND  MICROSCOPIC  FINDINGS
                               .   45  DAY SACRIFICE
    
                                  .   MALES  (cont.)
    
    Animal Ife.    Dose 6p.    Gross Observation        Microscopic  Observation
       2951       Op. 3       Mandibular LN-slightly
                             enlarged
    
                             Kidneys-pale
    
       2954       6p, 3       Kidneys-both pale
    
       2955       Gp. 3       Mandibular LN-enlarged
                             (8x4x3 mm)
    
                             P restate-Rt. lobe-enlarged
    
                             Kidneys-pale
    
       2956       Qp. 3       Rt. & Lt. kidney-pelvis
                             dilated
    
       2982       Gp. 4       Kidney-both pale
    
       2985       Op. 4       Kidneys-pale
    Lympnoid hyper plesia, moderate
    
    
    No cor responding lesion
    
    No corresponding lesion
    
    Lymphoid hyperplasia, moderate
    
    
    Dilation, gland, mild
    
    Nephropathy, chronic, minimal
    
    No cor responding lesion
    
    
    Nephropathy, chronic, minimal
    
    No corresponding lesion
                                         IV-49
    

    -------
                         GROSS  AND  MICROSCOPIC  FINDINGS
                                    45  DAY SACRIFICE
    
    
                                         FEMALES
    
    Animal  No.    DoseGiL   Gross  Observation         Hicrosmoic  Observation
       301?
      3118
    Gp.
    3020
    3046
    3052
    3079
    3082
    3083
    3085
    3087
    3088
    Op. 1
    Op. 2
    3p. 2
    Op. 3
    Sp.3
    Gp. 3
    Op. 3
    Op. 3
    Op. 3
    Gp. 4
    Kidneys-both pelvis
    dilated
    Rt & Lt. kidneys-pelvis
    dilated
    
    Liver-hernia (3x3x2mm)
    median lobe
    
    Mandibular Nodes-enlarged
    
    Kidneys-both pale
    
    Mandibular LN-enlarged
    (10x5x3mm)
    
    Mandibular LN-enlarged
    
    Kidneys-si ightly mottled
    
    Kidneys-slightly mottled
    
    Liver-Rt. lobe rounded
    edges (2.0x1.Ox 1.0cm)
    
    Lt Kidney-moderate
    enlargement of renal pelvis
    
    Rt kidney-minimal
    enlargement of renal pelvis
    Hydronephrosis, minimal
    One pelvis dilated. Other pelvis within
    normal range.
    
    Hydronephrosis, mild
    Lesion not identified in wet tissue.
    
    
    Lymphoid hyperplasia, mild
    
    No corresponding lesion
    
    Lymphoid hyperplasia, moderate
    
    
    Lymphoid hyperplasia, mild
    
    No corresponding lesion
    
    No corresponding lesion
    
    
    No corresponding lesion
    
    Hydronephrosis, multifocal, minimal
    
    
    Hydronephrosis, multifocal, minimal
                                         IV-50
    

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    V. QUALITY ASSURANCE REPORT
    

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    -------
    THIS PAGE REVISED
    
     ft   /i /)   il II study"°-
     (MM) 6 . UtUMlfW }
                           '
                                                                     1- 16- it,
                      QUALITY ASSURANCE STATEMENT
    
      This hlstopathology project has been conducted In compliance with Good
      laboratory Practice regulations promulgated oy the U. 5. Food  and Drug
      Administration and the U. 5. Environmental Protection  Agency.  Pathology
      Associates, incorporated  has  a  functioning  and responsive  quality
      assurance unit which has conducted appropriate inspections and reported
      all findings to management  The following is a record of those Inspections
      and reports:
    
    
                                                   Date Findings Reported
        Date of                                        to Management
      inspection*        Phase Inspected         and Study Pathologist
    **01-07-86           Tissue Trimming                     01-09-86
    **Q 1-09-86           Processing                         01-14-86
    **01-09-86           Embedding                          01-H-86
    * 02-19-86           Microtomy                         02-19-86
    * 02-19-86           Staining                           02-19-86
    * 02-19-86           Coverslipping                       02-19-86
    * 02-10-86           Labeling                           02-10-86
    **Q4-14-86           Individual Animal Data                 05-01-86
    **04-15-86           Data Entry                          05-01-86
    **04-15-86           Computer Validrtion                   05-01-86
    **04-23- 86           Dran Pathology Report                 05-01 -86
    **05-3Q-86           Final Pathology Report                 05-30-86
    **Q8-12-86           Revised Final Pathology Report           08-12-86
    *  General monthly phase inspection
    ** Inspection specific for Study Number
    fln accordance with the PA1 Quality Assurance Division's Standard Operating
    Procedures, phase inspections are routinely conducted on a random basis at a
    minimum  of  monthly.  Dates of  inspection are reported for  each  study
    according to the most recent phase inspection conducted during that period.
                                                   August 12, 1986
       : Director, Qualit^y4surance Unit                   Date
    
    
     "Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats."
      Study Number 5221.06
                                     V-l
    

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        APPENDIX 1
    
    
    
    
    REPORTS CODE TABLE
              v-L
    

    -------
    

    -------
       PATHOLOGY  ASSOCIATES, INC
    
                   ORTHO-CRE3QL
               STUDY NO. 5221.06
              SPRAGUE-DAWLEY  RATS
         Reports  Code  Table
    N    Tissues within  normal  histoiogical  limits
    
    A    Autolxsis precluding  a'dequate  evaluation
    
    U    Tissues unauai1able/unsuitab!e  for  evaluation
    
    S    Tissues not applicable  to  animal
    
    *    Tissues not examined/not  required bx  protocol
    I    mini mal
    
    2    mild
    
    3    moderate
    
    4    severe
    
    )    -focal
    
    ]    diffuse
    
    >    mu 1 t i focal
    
    P    Present
    
    B    Neoplasm, Benign
    
    M    Neoplasm, Malignant without Metastasis
    
    C    Neoplasm, Malignant with Metastasis
    
    X    Metastat ic Si te . <-O
    
    
              (End of Repor t)
    

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    -------
       APPENDIX 2
    
    
    
    
    ABBREVIATION LIST
    

    -------
    

    -------
                            ABBREVIATION LIST
    INFLAMMATION
    PERI VASCULAR
    MUSCLE
    EXTRAMEDULLARY HEMATOPOIES1S
    INTERSTITIAL
    LYMPH NODE
    INGUINAL
    EPITHELIAL
    LYMPHOCYTIC
    HARDERIAN GLAND
    INFLAM
    
    
    
    
    PERIV
    
    
    
    
    M.
    
    
    
    
    EMH
    
    
    
    
    INTERSTIT
    
    
    
    
    LN
    
    
    
    
    ING.
    
    
    
    
    EPITH.
    
    
    
    
    LYMPHOCY.
    
    
    
    
    HARD. GL.
                                    v-5
    

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              APPENDIX G
    
    
    PROTOCOL, AMENDMENTS AND DEVIATIONS
                                 MICROBIOLOGICAL
                                 ASSOCIATES INC.
    

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                                                   ORIGINAL
                                                Experiment Number 5221.06
    
                                                    Received  • by RA/QA
                  SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN
                           SPRAGUE DAWUEY RATS
     I.   PURPOSE
    
         The purpose of this study is to determine the toxic effects of
         o-cresol when administered by gavage for 13 weeks to Sprague Dawley
         rats.
    
    II.   SPONSOR AND TESTING FACIIJTY
    
         A.    Sponsor Name:  Research Triangle Institute (RTI)
    
         B.    Sponsor Authorization Date:  12 July 1985
    
         C.    Protocol Approval_ Date'  (See last page)
    
         D.    Testing Facility:  Microbiological Associates Inc.,
                                5221 River Road
                                Eethesda,  Maryland  20816
    
         E.    Princigal_Ir^/estiqator (Study=Dirict.Qr]_: Louis T. Mulligan,  Ph.D.
    
         F.    Toxicoloqist:  Earry S. Levine, D.Sc., D.A.B.T.
    
    III. TEST SCHECULE
    
         A,    Sctiedxiled Initiation Date*.  3 September 1985
    
         B,    Proposed Termination Date:  3 December 1985
                                     G - 2
                                      1
    

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                                                 Experiment Number 5221.06
    IV.  TEST ARTICLE
    
         A.   Name:   o-cresol
    
         B.   Source and Manufacturer
    
              Source:  Eastman Kodak Company
                       Rochester, NY 14650
    
              Manufacturer:  To be supplied
    
              Lot No.:   B-12-B
    
              Batch No.:   None
    
              Purity:  99% +
    
              In-house Chemical No.:   23
    
         C.   .Safety Precaut ions
    
              1.    Personnel Protection
    
                        Eye:  Safety goggles
    
                     Gloves:  Two pairs of gloves should be worn when
                              handling the neat chemical; one pair of
                              gloves should be worn when' handling dose
                              preparations,
    
                   Clothing:  Protective laboratory clothing will be
                              worn when handling dose preparations or
                              neat chemical,
    
                Ventilation:  Handling of open dosage containers
                              or chemical should be conducted in a
                              properly vented hood.
    
                 Respirator:  A respirator fitted with an organic
                              vapor (or organic vapor/acid vapor)
                              cartridge equipped with a particulate
                              filter will be used at all times when
                              working with open containers and when
                              working in roams with animals dosed
                              with this chemical.
                                      G - 3
                                       2
    

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                                  Experiment Number 5221.06
    Spillsand Leakage
    
    Persons not wearing the appropriate protective
    equipment and clothing should be restricted from
    areas of spills or leaks until cleanup has teen
    coupleted.
    
    If c-cresol or solutions of it are spilled the following
    steps should be taken:
    
    a.  Ventilate area of spill.  Eliminate all heat
        and ignition sources.
    
    b.  Use vermiculite, sodium bicarbonate, sand, or
        paper towels to absorb the oil.
    
    c.  Wash area with detergent and water or Mico-
        klene and water.  Rinse well with water.
    
    d.  Dispose of all material in the cleanup as
        hazardous waste,
    
    Waste and Disposal Procedures
    
    Securely package and label, in double bags, all
    solid waste material and dispose of by
    incineration or by burial at a secured landfill.
    Dispose of liquid waste in liquid hazardous waste
    drums.
    
    Preparation., of	Doses
    
    Doses will be prepared in the Carcinogen Handling
    Room, 3rd floor, 5221 River Road, Eethesda, MD. 20853.
                        G - 4
                        3
    

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                                                      Experiment Number 5221.06
                    5,  Analysis of .Solutions
                        The stability of the test solution will be determined
                        after storage for the same period and under the same
                        condition to be used in the study.
    
                        The accuracy of formulation will be checked by analysis
                        of samples taken from solutions prepared for administration
                        during weeks 1, 2, 4, 8 and 13 of treatment.
    
       V.   TEST SYSTEMS'
    
            A.  Animals
    
                1.  Strain/Species:  Sprague Dawley Eats
    
                2.  Number/Sex:  130 males/130 females
    
                3.  Age;  5-6 weeks old at start of dosing
    
                4.  Supplier:  Charles Mver Breeding Laboratories.
    
                5.  Justification of Test Animal:  The test animal  {Sprague
                    Dawley Rats) was specified by the sponsor and is a routine
                    laboratory animal utilized in small rodent subchronic toxicology
                    studies.
    
      VI.   HOUSING
    
            The animals will be individually housed in polycarbonate shoe boxes
            marked with a test article code and held on stainless steel racks
            equipped with an automatic watering system.  Heat treated hardwood
            chips will be used for cage bedding.  Racks will be periodically
            repositicned within the room to minimize any effect of variation in
            light intensity, temperature, etc.
    
    VII.    ANIMAL ENVIRONMENT
    
            A.  Temperature: 72° + 3°F
    
            B.  Humidity: 50 ± 15%
    
            C.  Light Cycle:  12 hour cycle
    
            D.  Water: _-Washington Suburban Sanitary Commission Potomac
                        Plant; untreated; ad libitum.
    
            E.  Feed:  Purina standard lab chow.
    
                                            G - 5
                                            4
    

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    VIII.
                                                      Experiment Number 5221.06
    
    
            F.  Cage Change ^ Schedule:  Cages will be changed every other weak.
    
            G.  Feeder Change Schedule:  Once weekly.
    
            H.  Rack Changes;  Every other week.
    
            I.  Air Change:  At least 12-15 per hour.
    
            ,J.  Bedding Changes:  Twice weekly.
    
            K.  Room Number:  Room #371
    
            L.  It is not expected that there are contaminants in the feed or
                water which would have any influence on the study.
            A.  Animals will be maintained in quarantine for 12-15 days.  The
                housing, cleaning, feeding and watering procedures will be the
                same as described above for the test period.
    
            B.  Animals will be observed twice daily for signs of illness or
                death and all unusual observations will be reported to- the Princiral
                Investigator or Director of Veterinary l-ledicine.
    
            C.  Animals will be examined during quarantine and approved for use
                by the Director of Veterinary Medicine prior to being placed on
                test.  Health Status Evaluation form RA/QA 11 will be completed
                by the Study Director and Director of Veterinary Medicine.
    
      IX.   RANDOMIZATION x ANIMAL NUMBERING >_ STATISTICAL ANALYSIS
    
            A.  Randomization:  During the quarantine period, the animals will be
                randomized as follows:  Starting with one sex of the species to be
                randomized, each animal will be weighed, placed into individually
                numbered cages and separated into one of a number of weight range
                groups which are based en successive intervals of 5 grams.  The
                weight of each is recorded on paper.  After all animals^have been
                placed into their appropriate weight range groups, 120 of the animals
                with weights closest to the median weight will be randomized.
                Outliers will be used for health check evaluation and baseline
                evaluations or killed.
    
                After the appropriate number of animals per sex have been selected,
                a random number table will be computer generated for each of the
                sexes.  After aniirals have been randomized to cages, a separate
                set of random numbers will be generated and used to allocate cages
                to a dose group.
    
                                           G - 6
                                            5
    

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                                                   Experiment Number 5221.06
    
    
         B.  Numbering:  Animals will be uniquely consecutively numbered using
             tee clips.
    
         C.  Statistics:  The data will be examined using analysis of variance
             techniques followed by a multiple conparison procedure for detecting
             differences between pairs of means.  Some pathology and clinical
             data may require nonparametric techniques to aid in interpretation.
    
    X.   EXPERMEOTAL METHODS
    
         A.  Dosing
    
             1.  Route:  Gavage (specified by sponsor)
    
             2.  Vehicle:  Corn Oil
    
             3.  Frequency;  Daily, approximately the same time each day,
                             7 days a week, for a total period of 13 weeks.
    
             4.  Dosage Volume:  Five (5) ml/kg calculated on animal's most recent
                                 bcdy weight.
    
             5.  Controls:   Receive vehicle alone at the same dosage volume
                             as treated animals.
    
             6.  Mixing Frequency:  Dosing solutions will be mixed on a weekly
                                    basis and kept refrigerated at 4°C.
                                         G - 7
                                         6
    

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                                              Experiment Nujrfcer 5221.06
    B.  Treatment _GrouPS
    
        Animals will be randomly assigned to groups with the following
        design:
                                                     Number of Animals
                                     Dose Level
        Group       Treatment       fang/kg/day)       Male       Female
    
          1      Negative control       —            30          30
    
          2          c-cresol           TBD         "30          30
    
          3          o-cresol           TBD            30          30
    
          4          o-cresol           TBD            30       '30
    
          5      Baseline clinical      	•            10          10
                     pathology
    
    
        The ten male and ten female animals in group §5 will be sacrificed
        prior to study initiation for collection of baseline data on
        hematology and serum chemistry.
    
        Ten male and ten female animals (selected prior to initiation of
        the study) from each remaining group will be sacrificed at 45-days
        post-treatment for clinical pathology and collection of tissues
        for possbile later evaluation.  The following organs will be
        weighed:  heart, liver, spleen, brain, kidneys (individually), gonads
        (individually), adrenals and thyroid/parathyroid.
    
    C.  Clinical Observations
    
        1.  Animals will be observed twice daily (once in the morning and
            once in afternoon) seven days per week for moribund!ty/mortality.
            Moribund animals unlikely to survive until the next observation
            will be sacrificed and necropsied immediately.
    
        2.  Each animal will be examined weekly for clinical signs of
            toxicity.
    
        3.  Signs of toxicity noted at other times will be recorded on
            room schedules and transferred to the observation sheet if they
            persist.
    
        4.  Animal Weights - Individual animal weights for test and control
            groups will be recorded at initiation (day 1) and weekly
            thereafter.
                                    G  - 8
                                    7
    

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                                              Experiment Number 5221.06
        5.  Individual feed, consumptions will be derived by calculating
            the difference in weight of each feed jar plus contents at
            the beginning and end of the feeding interval and dividing by
            the number of days involved.  An estimate of the mg of test
            material consumed/body weight/day will then be calculated,
    
    D.  OphthaImoscopv
    
        Funduscopic (indirect opthalmoscopy) and bicmicroscopic (slitlarnp)
        examinations will be performed pretreatment and at termination on
        all animals designated to be terminated at 13-weeks.
    
    E.  Clinical Pathology
    
        1.  The following hematolcgy (all animals fasted overnight) will
            be performed on the 20 animals designated for baseline values
            (day 1), on 10 males and 10 females/group designated to be
            sacrificed at 45 days and on 10 males and 10 females/group
            designated to be sacrificed at termination of the study:
    
            Hemoglobin
            Hematccrit
            Erythrocyte count
            Total and differential leukocyte count
            Flatlet count
            Reticulccyte count
    
        2.  The following clinical chemistry will be determined on serum
            samples per the hematology schedule:
    
            Sodium
            Chloride
            Potassium
            Phosphorus
            Blood creatinine
            co2
            SGPT
            SCOT:
            Glucose
            BUN
            Direct and total bilirubin
            SAP
            Total cholesterol
            Albumin
            Globulin
            Total protein
                                   G - 9
                                    a
    

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                                              Experiment Number 5221.06
        3.   Urinalysis will be determined on days 45 and 90- as outlined
            for clinical chemistry.   The following parameters will be
            measured:
    
            Specific gravity
            pH
            Protein
            Glucose
            Ketones
            Bilirubin
            Urobilinogen
            Microscopic examination
    
    F,  Necropsy and Histopathlogy:
    
        1.   A complete, detailed necropsy will be performed en all animals.
    
        2.   Animals that die or are sacrificed prior to the scheduled
            sacrifice will be necropsied as soon as possible after death.
            Animals that can not be necropsied immediately will be stored
            in a refrigerator until necropsy but no longer than 24 hours.
    
        3 .   From all animals on study, except those designated for baseline
            clinical chemistry the following tissues will be collected
            and preserved in buffered formalin.
    All gross lesions
    Brain (3 levels)
    Eye
    Pituitary
    Salivary gland
    Heart
    Thymus
    Thyroid (with parathyroid)
    Lungs (with mainstem bronchi)
    Trachea
    Esophagus
    Stomach
    Small and large intestine
    Adrenals
    Pancreas
    Liver
    Kidneys
    Urinary bladder
    Testes
    Prostate
    Ovaries
                                                    Corpus and cervix uteri
                                                    Spleen
                                                    Bone (with marrow)
                                                    Skeletal muscle .
                                                    Lymph node
                                                    Spinal cord
                                                    Mammary gland
                                                    Aorta
                                                    Sciatic nerve
                                   G - 10
                                    9
    

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                                              Experiment Number 5221.06
    
    
        4.  Histcpathoiogical evaluation will be performed on all abnormal
            tissues and lesions of all animals "on study.  All listed
            tissues will be saved from all rats at the 45-day sacrifice
            for possible future evaluation.  All the above listed tissues
            will be evaluated on all animals sacrificed because of a moribund
            condition, those that die on test, and all control and high-
            dose animals sacrificed at the 13 week termination.
            Histopathology in the mid and low dose groups will only be
            required for gross lesions and apparent target organs.   Target
            organs will be determined from previous studies, clinical
            data, and the histopathology in the high-dose level group.
            All lesions will be rated according to their severity.
    
        5.  At terminal sacrifice, in addition to terminal body weight,
            the heart, liver, spleen, brain, kidneys (individually),
            gcnads (individually), adrenals and thyroid/parathyroid will
            be weighed to three significant figures.  Organ weight to
            body weight ratios will be computed.
    
    G,  Statistical Procedures:
    
        In general, the data will be examined using analysis of variance
        techniques followed by a multiple comparison procedure for detecting
        differences between pairs of means.  Some anatomical and clinical
        pathology data may require nonparametric techniques to aid in
        interpretation.
    
    H.  Data Collections and Reporting:
    
        Abnormal observations, body weights, feed consumptions, dose
        formulation documentation, and general study comments will be
        recorded in bound laboratory notebooks.  Clinical laboratory data
        will be recorded in bound notebooks or will be direct  instrument
        or computer output.  Pathology data, including organ weights,
        will be recorded on individual loose-leaf pathology sheets  (one
        per animal).  At the completion of the study, all data and specimens
        will be transferred to the Quality Assurance Unit for storage  in
        the test laboratory archives.
    
        The following data will be collected and included in the final report:
    
        o Sections on introduction, materials and methods,  conclusions and
          discussion
        o Results of  all chemical analyses
        o Abnormal appearance or  behavior
        o Individual  and mean body weights initially and weekly through
          13 weeks
        o Results of  the ophthalmological examination
    
                                   G - 11
                                    10  .
    

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                                                      Experiment Number 5221.06
    
    
                o Individual and mean hematology, bleed chemistry and urinalysis
                  as outlined.
                o Individual and mean organ weights (heart, liver, spleen,  brain,
                  kidneys, gonads, adrenals, and thyroid/parathyroid)  from all
                  animals at termination
                o Individual necropsy observations of all animals
                o Individual histopathology of tissues as outlined.
    
       XI.  RECORDS TO BE MAINTAINED •
    
            All raw data pertaining to the conduct of this study including the
            final report will be retained as the regulations require in the archives
            at Microbiological Associates Inc., 5221 River Road, Bethesda,  MD
            20816.  If at some time in the future any of these data are to bs
            discarded, the sponsor will be first notified to obtain periirdssicn.
    
     XII.   STANDARD OPERATION PROCEDURES AND PROTOCOL ALTERATION
    
            All procedures not specified in this protocol will be performed in
            accordance with the Microbiological Associates Inc.  Standard Operating
            Procedures' Manual and in compliance with the FDA's Good Laboratory
            Practice Regulations.
    
            Alterations of the study tray be made after the study has been initiated.
            In the event that the sponsor verbally authorizes a change in protocol,
            such change will be honored by Microbiological Associates Inc.  However,
            it is then the responsibility of the sponsor to produce written
            verification of the verbal authorization, which will result in the
            issuance of an official protocol amendment.
    
    XIII.   REPONSIBILTTTES
    
            1.  L.T, Mulligan, Ph.D:  Principal Investigator/Study Director
    
            2.  Barry S-. Levins, D.Sc., D.A.B.T.:  Toxicologist
    
            3.  Lucas H. Brennecke, V.M.D., Ph.D.:  Veterinary Pathologist
    
            4.  John Miller, DVM, AGLAM:  Laboratory Animal Veterinarian
    
            5.  Harold J. Paulin, M.S., Chemist
    
            6.  Jean L. Causer, B.S.:  Operations Supervisor
    
            7,  Nona S. Karten, M.A.:  Quality Assurance
                                           G -  12
                                            11
    

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                                                      Experiment Number 5221.06
     XIV.   REFERENCES
            1.  "Guidelines for Carcinogen Bioassay in Small Rodents",  Sontag,
                J.M., Page, N.P., and Saffiotti, U., NCI, DHEW Publication No.
                (NIH) 78-801.
    
            2.  Contract with Research Triangle Institute.
    L.T. Mulligan) Ph.D.    '
    Principal Investigator
    Sponsor
                -? SC-l •
                ' ^'ifi
    Date
     Date
                                           G - 13
    
                                            12
    

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                              mCTQCQL AMENDMENT
                                                      ORIGINAL
    Date:  July 24, 1936
    
    Study No.;   5221.06
    
    Title;  Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Eats
    
    
    Amendment:
    
    
    18.  Page 8,  Part X, Section D;
    
        Delete "and biomicroscopic  (slitlaitp)".
    
        Reason:  Incorrect in protocol; it was never intended to be done by the
        ophthalmologist.
           Study(Director//Dat
          Sponsor Approval      ^~"^             Date
                                                        X; MICROBIOLOGICAL
                                                           ASSOCIATES INC.
    

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                               PRC'IOCOL AMENDMENT
            OR  G  NA!
    Date:  July 24,  1986
    
    Study No.:   5221.06
    
    Title:  Subchronic Toxicity of Ortha-Cresol in Sprague Dawley Rats
    
    
    Amendment;
    
    17.  Page 6, Part X, Section A, No. 3:
    
        "for a total period of 13 weeks"  should read "for a period of thirteen
        weeks or until sacrifice,
    
        Reason:   Required due to staggered sacrifice schedule.
           Sponsor Approval
                                             /Date1
    
                                             °l
    te
                                       G - 15
                                                             MICROBIOLOGICAL
                                                             ASSOCIATES INC.
    

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                                PROTOCOL AMENDMENT
                                                            OR  G  M/
    Date:  July 24, 1986
    
    Study No.:  5221.06
    
    Title;  Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
    
    
    Amendment:
    16.  The interim sacrifice was conducted over a two-day period (test days 46
         and 47), and the terminal sacrifice was conducted over a three-day period
         (test days 92, 93 and 94).
    
         Reason:  The large number of animals in the study did not allow
         necropsies and clinical pathology evaluations to be conducted in one day
         at either the interim or terminal sacrifice.
            Study Director  /                   /Date
           Sponsor Approval                      Date
                                                               MICROBIOLOGICAL
                                                               ASSOCIATES INC.
    

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                                                      Experiment Number 5221.06
                                  PROTOCOL AKENTMENT
    Date:  September 13, 1985
    
    Study Number:  5221.06
    
    Title;  Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
    
    
    
    Mendment:
    
    
    1.  Page 1 Part III Section A Scheduled Initiation Date: 16 September 1985.
    
                        Section B Proposed Termination Date: 16 December 1985.
    
        Reason:  Delay in start due to original animals being found unhealthy.
    
    2.  Page 4 Part V Section A No. 4 Supplier:  Charles River Breeding Laboratories
                                                 lakeview, NY
    
        Reason:  Source not stated in protocol.
    
    3.  Page 5 -Part VIII Section A:  Add the following sentence at the end.
                                    "Animals were group housed during the quarnatine
                                     period but individually housed at test animal
                                     section."
        Reason:  Omitted in protocol.
    
    4.  Page 6 Part X Section A No. 6:  Dosing solutions will not be refrigerated.
    
        Reason:  Refrigeration not necessary and may cause the test article to come
                 out of solution.
    
                                                                Dose levels
    5.  Page 7 Part X Section B Treatment Groups:  Group        fmq/kq/davl
    
                                                     2               50
                                                     3              175
                                                     4  '            600
    
        Reason:  Not stated in protocol.
                                               17
    

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                                                      Experiment Number 5221.06
    6.  Page 7 Part X Section C No.2: Clinical Observations:  Change "examined
                                      •  weekly" to "examined daily."
    
        Reason:  Incorrect in protocol.
    
    7.  Page 8 Part X Section C No. 5;  The following senctence is to be deleted
                                        from the protocol.  "An estimate of the
                                        mg of test material consumed/body
                                        weight/day will then be calculated."
    
        Reason;  Not a diet study.
    
    8.  Page 10 Part X Section H Data Collections and Reporting:  The word "bound"
                                        is deleted from the phrase "bound notebooks,"
    
        Reason:  Some notebooks are loose-leaf.
    Study Directr          /      '            Date    V
                  ^^
    to
    Sponsor Approval                           Date
                                               18
    

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                                                              ORIGINAL
                                PROTOCOL AMENDMENT
    Date:  Septeiriber 13, 1985
    
    Study Number:   5221.06
    
    Title:  Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Bats
    
    
    
    Amendment;
    1.  Page 7,  Part X, Section B: _ Treatment Groups:  Change 'the phrase
        "post-treatment" to "post-treatment initiation"  in the first sentence of
        the last paragraph.
    
        Reason:   Omitted in protocol.
    
    2.  Page 7,  Part X, Section C,  No.  2: Clinical Observations:  Change "examined
        daily" to "examined weekly."
    
        Reason:   Incorrect in protocol.
    
    
    3.  Page 8,  Part X, Section E,  No.  2: Clinical Pathology:  Add Calcium.
    
        Reason:   Sponsor request.
    Study Direcor
    Sponsor Approval                          Date
                                         G - 19
    

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                                                               ORIGINAL
                                PROTOCOL AMENEMENT
    Date:   October, 2, 1985
    
    Study Number:  5221.06
    
    Title;  Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
    
    
    
    fonendment:
    4.  In anticipation of testing rats for the neurotoxic effects of o-cresol,
        3 rats/sex/dose were added on Test Day 1.  It was subsequently decided
        that a separate experiment to test for these effects "would be performed.
        Therefore, these extra animals will be eliminated from study.
    
    5.  To facilitate animal identification, ear tags were attached to test
        animals.  These will be included with necropsy test specimens.
    Study Director      f            ,        Date
    Sponsor Approval                          Date
                                       G-20
    

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                                                            ORIGINAL
                                 PRDIDCOL AMENEMENT
    
    
    Date:  Ocrtober 16,"  1985
    
    Study Number:   5221.06
    
    Title:  Subchronic  Toxieity of Ortho-Cresol  in Sprague Dawley Rats
    
    
    
    
    Amendment:
        Page 7,  Part X, Section B, Treatment Groups:  Delete the following sentence.
        "The following organs will be weighed:  heart, liver, spleen,  brain,
        kidneys (individually), {jgori5das} (individually), adrenals and thyroid/
        parathyroid."             O^JMA^S C££t
    
        Reason:   Per discussion with the Sponsor, organ weights are not necessary
                 at the 45-day interim kill.
    
        Page 8,  Part X, Section E No, 1: Md prothrombin time (PT)  and activated
        partial thromboplastin time  (APTT),  and delete platelet count.
    
        Reason;   PT and APTT are better estimates of clotting potential than
                 platelet count.
    Study Director                            Date
    Sponsor Approval                          Date
                                        G-21
    

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                                                                 ORIGINAL
                                 PROTOCOL MEMDXENT
    
    Date:  November 26,"  1985
    Study Number:   5221.06
    Title:  Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
    Amendment:
              d
     9.  Page ?,  Part VII, Section E, Feed:  Substitute  "Purina standard lab
         chow" with "Purina Rodent Chow No, 5001",
         Reason:   Omitted in protocol.
    10.  Page 5,  Part VII, Section K, Room Number:   change "Room #371" to
         "Room #373"
         Reason:   Incorrect in protocol.
    11.  Page 5,  Part VIII, Quarantine/ Section B:   Unusual observations
         during the quarantine period can also be reported to the Study Toxicologist.
         Reason:   Omitted in protocol.
    12.  Page 9,  Part X,  Section F, No. 2:  If necessary, animals which die on
         test are stored  in a refrigerator until necropsy but no longer than 16 hours.
         Reason:   Incorrectly stated as 24 hours in protocol.
    13.  Page 11,  Part XIII, No. 3:  Change the Veterinary Pathologist to
         Dr.  Diana Copeland, Diplomats, ACVP.
         Reason:   This is necessary to finish all four RTI study reports on time.
          Director       1                    Date"<•
    Sponsor Approval          '                Date
                                       G-22
    

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                                                              Protocol Deviations Incurred During Conduct of Study 5221.06
    9
    Date
    
    9/17/85
    
    
    9/11/85, 12/12/85
    
    
    9/17/85
    
    
    
    9/30/85-10/7/85
    
    
    Various days
    
    
    Duration of study
    
    
    Duration of study
    
    
    Various days
    
    
    Various days
                             Deviation                              Effect on Study
    
    Baseline serun phosphorus and electrolytes;  blood prothroibfn         None
    time and activoted prothrombin tine were not measured.
    
    Bi microscopic examinations not performed during the                  Hone
    pretreatment and pretermination ophthalmic examinations.
    
    Three animals were stored In the freezer Instead of in                None
    the refrigerator between the time of death and the tine
    of necropsy.
    
    Feeders changed weekly with the exception of week 3 in                None
    which some were not changed.
    
    Ho documentation was made concerning dosing  for two                   None
    females.
    
    No documentation was made concerning the time  of day                  Hone
    when dosing was performed.
    
    Ho documentation was made concerning rack, feeder or                  None
    cage bedding changes.                .                             .         ,
    
    Animal room temperatures out of recommended  range on                  None
    69 days.
    
    Animal room humidity was out of recofmended  range on                  None
    27 days.
    

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